5617 results for "canc*"

in 48.09 milliseconds.

• Sequencing_of_rare_human_histiocytic_tumour

  Sequencing of rare human histiocytic tumour

  Study EGAS00001000591

• Angiosarcoma_RNA_sequencing

  Extension of angiosarcoma whole genome sequencing study

  Study EGAS00001000590

• Chordoma_Sequencing_Project_Whole_Genome

  This is a continuation of the Chordoma Sequencing Project, prelim #G0175-122-CF. All cancers arise due to somatically acquired abnormalities in DNA sequence. Systematic sequencing of cancer genomes allows acquisition of complete catalogues of all classes of somatic mutation present in cancer. These mutation catalogues will allow identification of the somatically mutated cancer genes that are operative and characterise patterns of somatic mutation that may reflect previous exogenous and endogenous mutagenic exposures. In this application, we aim to perform whole genome sequencing on 10 chordoma matched genome pairs. The Chordoma Foundation will fund the RNA Sequencing/Methylation and SNP6 costs for this project while the whole genome and library sequencing will be covered under the CGP, 2012-2013 core WTSI internal funding. An additional sequencing of three cancer cell lines will be added to this work, financed by the Chordoma Foundation. In this project, the Chordoma foundation will pay for the additional costs of methylation, RNA Seq,

  Study EGAS00001000409

• Breast_Cancer_Sequential_Sampling_Targeted_Capture

  This study aims to target capture sequence regions of interest from DNA derived from breast cancer patients who received neo-adjuvant chemotherapy. All patients had multiple biopsies performed before chemotherapy. Patients who had residual disease after the course of treatment underwent a further biopsy. We aim to characterise the mutations involved.

  Study EGAS00001000596

• Chordoma_Sequencing_Project_RNAseq

  This is a continuation of the Chordoma Sequencing Project. All cancers arise due to somatically acquired abnormalities in DNA sequence. Systematic sequencing of cancer genomes allows acquisition of complete catalogues of all classes of somatic mutation present in cancer. These mutation catalogues will allow identification of the somatically mutated cancer genes that are operative and characterise patterns of somatic mutation that may reflect previous exogenous and endogenous mutagenic exposures. In this application, we aim to perform whole genome sequencing on 10 chordoma matched genome pairs. RNA Sequencing/Methylation and SNP6 and an additional sequencing of three cancer cell lines will be added to this work.

  Study EGAS00001000410

• GEL_WGS_Comparison

  These samples are to be analysed with the CGP Developed cancer panel and the results will be compared with WGS data from 4 different comercial providers.

  Study EGAS00001000649

• Mutational_Signatures_of_relapse_in_rectal_cancer_FFPE_samples_in_the_CR07_clinical_trial

  The CRO7 clinical trial recruited patients with clinically operable rectal adenocarcinoma. Patients were randomized to either pre-operative short course surgery followed by chemo-radiotherapy only in those patients at high risk of local relapse. Patients in both arms the received standard %-FU based adjuvant chemotherapy as per local policy. We intend to use FFPE derived DNA from the primary tumours to identify patterns of mutations or copy number alterations that are predictive of local or distant relapse.

  Study EGAS00001000651

• Harnessing_transposons_for_drug_resistance_gene_discovery_in_cancer

  This study involves a forward genetic screen to identify common insertion sites in drug resistant clones. We will be utilising piggybac transposon systems in order to generate multiple drug resistant clones in a range of human cancer cell lines.

  Study EGAS00001000468

• Molecular Signature of Saudi Thyroid Cancer Using whole exome sequencing

  In Saudi Arabia, thyroid cancer ranked second only to breast cancer among females, eleventh among males and this increased incidence is prevalent in other Gulf Council Countries also. Differentiated thyroid cancer, which includes papillary thyroid cancer (PTC) and follicular subtypes, accounts for 90% of all thyroid malignancies. Currently, there are no clinical or molecular diagnostic tools to predict recurrence and aggressiveness of a subset of PTC. With the goal of better understanding the pathobiology of thyroid carcinogenesis we will use Whole Exome Sequencing to decipher the molecular and genetic signature of Saudi PTC based on International Cancer Genome Consortium (ICGC) Guidelines. The study will provide a better understanding of PTC and should have important clinical implications in the development of new and better strategies for targeted therapeutic intervention for the treatment of Saudi Arabian PTC

  Study EGAS00001000680

• MPN_mutation_order_followup

  To evaluate the presence of mutations in frequently mutated genes in MPN by performing targeted resequencing of a selected gene panel comprising of 111 genes across 40 samples with MPN.

  Study EGAS00001000663

• Bone_Cancer___Rare_Types_Whole_Genome

  We propose to definitively characterise the somatic genetics of a selection of rare bone cancers through generation of comprehensive catalogues of somatic mutations by high coverage genome sequencing.

  Study EGAS00001000501

• Whole genome and transcriptome analysis of a sporadic and recurring parathyroid carcinoma

  Parathyroid carcinoma is an extremely rare endocrine malignancy with an estimated incidence of less than 1 per million population. Excessive secretion of parathyroid hormone, extremely high serum calcium level and the deleterious effects of hypercalcemia are the clinical manifestations of the disease. Up to 60% of patients develop multiple disease recurrences and although long-term survival is possible with palliative surgery, permanent remission is rarely achieved. Molecular drivers of sporadic parathyroid carcinoma have remained largely unknown. Previous studies, mostly based on familial cases of the disease, suggested a potential role for the tumor suppressor MEN1 and proto-oncogene RET in benign parathyroid tumorigenesis while the tumor suppressor HRPT2 and proto-oncogene CCND1 may also act as drivers in parathyroid cancer. Here, we report the complete genomic analysis of a sporadic and recurring parathyroid carcinoma. Mutational landscapes of the primary and recurrent tumor specimens were analyzed using high throughput sequencing technologies. Such molecular profiling allowed for identification of somatic mutations never previously identified in this malignancy. These included single nucleotide point mutations in well characterized cancer genes such as mTOR, MLL2, CDKN2C and PIK3CA. Comparison of acquired mutations in patient-matched primary and recurrent tumors revealed loss of PIK3CA activating mutation during the evolution of the tumor from the primary to the recurrence. Structural variations leading to gene fusions and regions of copy loss and gain were identified at a single-base resolution. Loss of short arm of chromosome 1 along with somatic mis-sense and truncating mutations in CDKN2C and THRAP3, respectively, provide new evidence for the potential role of these genes as tumor suppressors in parathyroid cancer. The key somatic mutations indentified in this study can serve as novel diagnostic markers as well as therapeutic targets.

  Study EGAS00001000484

• Whole exome sequencing of 103 pairs BLCA-CN

  We sequenced 50M exomes of 103 pairs bladder cancer of chinese

  Study EGAS00001000677

• FFPE_CPA_Accreditation_Study__Part_2

  FFPE CPA accreditation of genome-scale sequencing in routinely collected formalin-fixed paraffin-embedded (FFPE) cancer specimens versus matched fresh-frozen samples using targeted pulldown capture prior to Illumina sequencing.

  Study EGAS00001000692

• BRAF_and_MEK_resistant_cell_line_clones

  The Sanger Institute has the largest collection of genetically-characterised cancer cell lines world-wide (we have collected >1000 human cancer cell lines which are being screened against >400 cancer therapeutics (http://www.sanger.ac.uk/genetics/CGP/translation). These lines have been characterized to the level of gene copy number, gene expression and cancer gene mutation sequence data. This has enabled us to select melanoma lines with varying BRAF mutational status and that show sensitivity to a range of BRAF inhibitors. Sensitive lines are being used to generate resistant clones by serial exposure to increasing concentrations of BRAF and MEK inhibitors and these are being characterised by genome-wide copy number analysis as well as by whole exome sequencing.

  Study EGAS00001000172

• Use_of_Deep_Sequencing_to_Dectect_Clonal_Mutations_In_Sun_Exposed_Skin_Epidermis

  This study aims to define the landscape of somatic mutations in sun exposed human skin by deep sequencing, analyse their frequency and use the data to infer the effect of mutations on proliferating cell behaviour. The frequency of each mutation will reflect the size of the clone of cells in the tissue sample. By analyzing small samples, clones with as few as 100 cells will be detectable. Allele frequency distributions for each mutation will be used to infer cell fate using published methods (Klein et al. 2010). This study will shed unprecedented light on the early clonal events that lead to the emergence of cancer.

  Study EGAS00001000515

• Chondromyxoid_fibroma

  Chondromxoid fibroma is a benign tumour of bone with unknown underlying pathogenesis. To determine pathognomic genomic event in chondromyxoid fibroma whole genome sequencing will be undertaken to reconstruct rearrangements and find underlying mutations.

  Study EGAS00001000533

• Distinct evolutionary trajectories of primary high grade serous ovarian cancers revealed through spatial mutational profiling

  High-grade serous ovarian cancer (HGSC) is characterized by poor outcome, often attributed to emergence of treatment-resistant sub-clones. We sought to measure the degree of genomic diversity within primary, untreated HGSC to examine the natural state of tumor evolution prior to therapy. We performed exome sequencing, copy number analysis, targeted amplicon deep sequencing and gene expression profiling on thirty-one spatially and temporally separated HGSC tumor specimens (six patients) including ovarian masses, distant metastases, and fallopian tube lesions. We found widespread intra-tumoral variation in mutation, copy number, and gene expression profiles, with key driver alterations in genes present in only a subset of samples (e.g. PIK3CA, CTNNB1, NF1). On average, only 51.5% of mutations were present in every sample of a given case (range: 10.2% to 91.4%), with TP53 as the only somatic mutation consistently present in all samples. Complex segmental aneuploidies, such as whole genome doubling, were present in a subset of samples from the same individual, with divergent copy number changes segregating independently of point mutation acquisition. Reconstruction of evolutionary histories showed one patient with mixed HGSC and endometrioid histology with common etiologic origin in the fallopian tube and subsequent selection of different driver mutations in the histologically distinct samples. In this patient, we observed mixed cell populations in the early fallopian tube lesion, indicating diversity arises at early stages of tumorigenesis. Our results reveal that HGSC exhibit highly individual evolutionary trajectories and diverse genomic tapestries prior to therapy, exposing an essential biological characteristic to inform future design of personalized therapeutic solutions and investigation of drug resistance mechanisms.

  Study EGAS00001000547

• CPC-GENE Prostate Cancer Heterogeneity Study

  Herein we describe a molecular portrait of potentially curable, Gleason 7 and intermediate risk prostate cancer based on genome-wide CNV profiles of 96 patients, and subsequent whole-genome sequencing of 28 tumours from 10 patients, using DNA quantities that are achievable in diagnostic biopsies (50 ng). We show that Gleason 7 cancer is highly heterogeneous at the SNV, CNV, and intra-chromosomal translocation levels, and is characterized by a very low number of recurrent SNVs but significant structural variation. We identified a novel recurrent MYCL1 amplification, which was strongly associated with TP53 deletion and prognostic for biochemical recurrence in this cohort. Moreover, we identified clear evidence of divergent tumour evolution in multi focal cancer and, in 2/5 cases evaluated, multiple tumours of independent clonal origin. Taken together, these data represent the first systematic evaluation of the differential genomics of potentially curable prostate cancer, and strongly suggest that a more robust understanding of the relationship between genetic heterogeneity and clinical outcomes is required to effectively develop biomarkers of prognosis based on tumour genomics.

  Study EGAS00001000549

• Hypermutation of the inactive X chromosome is a frequent event in cancer

  Mutation is a fundamental process in tumorigenesis. However the degree to which the rate of somatic mutation varies across the human genome and the mechanistic basis underlying this variation remain to be fully elucidated. As part of the ICGC PedBrain and Malignant Lymphoma (MMML-Seq) consortium we performed a cross-cancer comparison of whole genomes comprising a diverse set of childhood and adult tumors including both solid and hematopoietic malignancies. In addition we performed whole genome sequencing of clonally expanded hematopoietic stem/progenitor cells (HSPCs) from healthy individuals to compare somatic mutation rates.

  Study EGAS00001000565

• RB1 Gene Inactivation by Chromothripsis in Human Retinoblastoma

  Retinoblastoma is a rare childhood cancer of the developing retina. Most retinoblastomas initiate with biallelic inactivation of the RB1 gene through diverse mechanisms including point mutations, nucleotide insertions, deletions, loss of heterozygosity and promoter hypermethylation. Recently, a novel mechanism of retinoblastoma initiation was proposed. Gallie and colleagues discovered that a small proportion of retinoblastomas lack RB1 mutations and had MYCN amplification [1]. In this study, we identified recurrent chromosomal, regional and focal genomic lesions in 94 primary retinoblastomas with their matched normal DNA using SNP 6.0 chips. We also analyzed the RB1 gene mutations and compared the mechanism of RB1 inactivation to the recurrent copy number variations in the retinoblastoma genome. In addition to the previously described focal amplification of MYCN and deletions in RB1 and BCOR, we also identified recurrent focal amplification of OTX2, a transcription factor required for retinal photoreceptor development. We identified 10 retinoblastomas in our cohort that lacked RB1 point mutations or indels. We performed whole genome sequencing on those 10 tumors and their corresponding germline DNA. In one of the tumors, the RB1 gene was unaltered, the MYCN gene was amplified and RB1 protein was expressed in the nuclei of the tumor cells. In addition, several tumors had complex patterns of structural variations and we identified 3 tumors with chromothripsis at the RB1 locus. This is the first report of chromothripsis as a mechanism for RB1 gene inactivation in cancer.

  Study EGAS00001000598

• PLCRC_study

  Genomic libraries (500 bps) will be generated from total genomic DNA derived from Colorectal cancer patients and subjected to short paired end sequencing on the llumina platform. Paired reads will be mapped to build 37 of the human reference genome to facilitate the generation of genome wide copy number information, and the identification of novel rearranged cancer genes and gene fusions.

  Study EGAS00001000612

• Osteosarcoma_RNAseq

  We propose to definitively characterise the somatic genetics of Osteosarcoma cancer through generation of comprehensive catalogues of somatic mutations by high coverage genome and transcriptome sequencing.

  Study EGAS00001000615

• Combination_therapies_for_personalized_cancer_medicine

  It is the ambition of the team formed by members of the Netherlands Cancer Institute (NKI) and the Cancer Genome Project at the Wellcome Trust Sanger Institute (WTSI) to unravel the genomic and phenotypic complexity of human cancers in order to identify optimal drug combinations for personalized cancer therapy. Our integrated approach will entail (i) deep sequencing of human tumours and cognate mouse tumours; (ii) drug screens in a 1000+ fully characterized tumour cell line panel; (iii) high-throughput in vitro and in vivo shRNA and cDNA drug resistance and enhancement screens; (iv) computational analysis of the acquired data, leading to significant response predictions; (v) rigorous validation of these predictions in genetically engineered mouse models and patient-derived xenografts. This integrated effort is expected to yield a number of combination therapies and companion-diagnostics biomarkers that will be further explored in our existing clinical trial networks.

  Study EGAS00001000655

• Breast Cancer Follow Up Series

  This study's purpose is to use data generated in whole genome and exome Breast Cancer sequencing to target specific areas in multiple other Breast Cancer samples. These areas will then be subjected to PCR in multiple cases, tagged and then pool the resultant amplicons. These amplicons will then be sequenced on the Illumina GAII. This is hoped to show the prevalence of previous findings in multiple individuals in a high throughput method.

  Study EGAS00001000002

• Exploration of CNV’s and SNV’s in cancers with well-known genetic rearrangements: Identification of additional genetic changes in rearrangements-driven cancer

  Specific cancers are well known to have specific gene rearrangements. Representative cancer is chronic myeloid leukemia (CML) which is famous for BCR/ABL gene rearrangements. By the way, also genetic rearrangements are not infrequently found in acute leukemia, and those include CBFB/MYH11 rearrangements, PML/RARA rearrangements, AML/ETO rearrangements, and BCR/ABL rearrangements. The situation is same is for lung adenocarcinoma of non-smokers and prostate cancers, and ALK and RET gene rearrangements are recently found. However, not all these rearrangements are sufficient to develop cancer, and it is suggested that some genetic aberrations are required for the development and progression of cancer in addition to these genetic rearrangements. In this study, we have a plan to explore the existence of additional genetic changes including single nucleotide variants (SNV’s) and copy number variations (CNV’s) in cancers with specific genetic rearrangements so as to define additional genetic changes that confer full oncogenic potential to cancer cells. So as to look at SNV’s and small indels, we are going to use whole exome sequencing (WES) data. And as for CNV’s, we are going to use array-CGH data. Also, to check the functionality of these genetic changes, we are going to use whole transcriptome data (WTS). In addition, in samples with whole genome sequencing (WGS ) data, we are going to explore genetic changes in intronic regions also. In fact, we sequenced 10 AML samples which are known to have specific genetic rearrangements. Analysis of these WGS, WES and WTS data are under the way. If we have a chance to access WES, array-CGH and WTS data of other cancer samples with specific genetic rearrangements, we would be able to compare additional genetic changes required for oncogenesis in cancer cells with various genetic rearrangements. We hope this result will enlighten our understanding of cancer genetics further.

  Study EGAS00001000673

• WGS of liver cancer in the Japanese population

  Hepatocellular carcinoma (HCC) is the third leading cancer-related cause of death and the seventh most common form of cancer worldwide, with an estimate of more than 700,000 new cases each year. The most established risk factors of HCC are chronic HBV and HCV infection. HBV infection is responsible for over 50% of the worldwide attributable risk of HCC, especially in East Asia and Africa, while in Japan and several Western countries HCV infection is the most common risk factor for HCC. To gain insights into the molecular alterations of virus-associated HCC, we performed whole genome sequencing (WGS) of 321 HCC tumors from 159 patients. This work was performed as a part of the ICGC (International Cancer Genome Consortium) project.

  Study EGAS00001000678

• Epigenetic Intratumor Heterogeneity and Clonal Evolution in Aggressive Prostate Cancer

  Our study investigated the spatial epigenome variation within 5 aggressive prostate adenocarcinomas.

  Study EGAS00001000682

• A Comprehensive Catalogue of Somatic Mutations from a Human Cancer Genome

  We have carried out complete sequencing of the genome of the human male maligant melanoma cell line COLO-829 using the Illumina Genome Analyzer II. We generated a sequencing library with a median insert size of ~200 bp following random fragmentation and gel fractionation of the genomic DNA. We sequenced 75 bases from both ends of these templates to cover the COLO-829 genome to an average depth of more than 40x. We have carried out purity-filtering (PF) to remove mixed reads, where two or more different template molecules are close enough on the surface of the flow-cell to form a mixed or overlapping cluster. No other filtering of the data has been carried out prior to submission. We have also submitted sequence data for a lymphoblastoid control cell line COLO-829BL from the same individual.

  Study EGAS00000000052

• Multifocal_Breast_Project

  Comparison of genomic rearrangements and DNA methylationpatterns between different foci of multiple synchronous(multifocal and multicentric) invasive breast cancers

  Study EGAS00001000004

• Chondrosarcoma_Exome_

  Agilent whole exome hybridisation capture will be performed on genomic DNA derived from Chondrosarcoma cancer and matched normal DNA from the same patients. Next Generation sequencing will be performed on the resulting exome libraries and mapped to build 37 of the human reference genome to facilitate the identification of novel cancer genes

  Study EGAS00001000038

• Kaposi_sarcoma_exome

  Agilent whole exome hybridisation capture will be performed on genomic DNA derived from Kaposi sarcoma cancer and matched normal DNA from the same patients. Next Generation sequencing will be performed on the resulting exome libraries and mapped to build 37 of the human reference genome to facilitate the identification of novel cancer genes

  Study EGAS00001000032

• 1__Fanconi_Anemia_transformation_to_AML

  Genomic libraries (500 bps) will be generated from total genomic DNA derived from 7 Fanconi anemia (FA) derived Acute myeloid leukemia samples and subjected to total of two lanes of 50 bp, paired end sequencing on the llumina HiSeq. Paired reads will be mapped to build 37 of the human reference genome to facilitate the generation of genome wide copy number information, and the identification of novel rearranged cancer genes and gene fusions.

  Study EGAS00001000033

• Lung_Cancer_Whole_Genomes

  We propose to definitively characterise the somatic genetics of Lung cancer through generation of comprehensive catalogues of somatic mutations by high coverage genome sequencing.

  Study EGAS00001000148

• Genome Landscape of Primary Pancreatic Ductal Adenocarcinoma

  The purpose of the Australian ICGC Pancreatic Cancer Genome Sequencing Initiativestudy is to identify the common driving mutations underlying the initiation anddevelopment of Pancreatic Adenocarcinoma in a large cohort of pancreatic cancerpatients (n=350). Matched genome sequences will be generated from normal tissue(duodenum) and resected primary tumour tissue in each patient using exome andwhole genome sequencing. The complete repertoire of somatic mutations will bedetermined (substitutions, indels, copy number changes and structural changes).Where possible, matched transcriptome sequencing will also be carried out todetermine locus activity, which mutations are actively expressed and whichrearrangements give rise to gene-fusion transcripts.

  Study EGAS00001000154

• ALK_inhibitors_in_the_context_of_ALK_dependent_cancer_cell_lines

  Anaplastic lymphoma kinase (ALK) has recently been found to be a critical cancer gene in cases of lung cancer, neuroblastomas and lymphomas. ALK inhibitors have recently shown significant activity in lung cancer patients with tumours that harbour the EML4-ALK gene rearrangement, but already drug-resistance is emerging. We have taken a lung cancer cell line H3122 (with the EML4-ALK rearrangement) and generated clones resistant to a small molecule inhibitor of ALK by serial exposure to the drug over 8 weeks. We now wish to characterise at the exome level whether the acquisiton of resistance has been accompanied by the development of new mutations that we can take forward for further study as the potential mechansims underlying the resistance. We therefore propose to exome sequence the parental NCI-H3122 cell line as well as drug-resistant clones.

  Study EGAS00001000082

• Linking genes, genomic instability and molecular subgroups in medulloblastoma

  Brain tumors are the second most common pediatric cancer and carry the highest mortality rates in this age group. Medulloblastoma is the most frequent malignant brain tumor of childhood. Recent studies indicate that medulloblastoma comprises at least four sub-entities (SHH-signaling, WNT-signaling, Group-C, Group-D) that differ in molecular alterations, cell of origin, clinicopathological features and outcome. Further characterization of the entire spectrum of genomic alterations underlying the formation of these distinct groups is urgently needed to identify diagnostic and prognostic biomarkers for clinical management and uncover novel therapeutic targets.

  Study EGAS00001000085

• Familial_Thrombocytosis_germline_exome_sequencing

  Agilent whole exome hybridisation capture will be performed on genomic DNA derived from 3 relatives from a family with multiple affected familial thrombocytosis (FT) patients. Germline DNA from 2-4 patients affected with FT will be used to prepare libraries and sequenced in one lane of HiSeq sequencing, mapped to build 37 of the human reference genome to facilitate the identification of novel cancer genes.

  Study EGAS00001000088

• PREDICT

  PREDICT/Predicting individual response and resistance to VEGFR/mTOR pathway therapeutic intervention using biomarkers discovered through tumour functional genomics.

  Study EGAS00001000094

• Myeloproliferative_Disorder_Sequencing

  Agilent whole exome hybridisation capture will be performed on genomic DNA derived from 50 myeloproliferative disorder samples and matched normal DNA from the same patients. Three lanes of Illumina GA sequencing will be performed on the resulting 100 exome libraries and mapped to build 37 of the human reference genome to facilitate the identification of novel cancer genes. In addition, 500bp, NO_PCR total genomic libraries will be prepared from the same samples and five lanes of Illumina GA sequencing will be analysed to characterise genome wide, somatically acquired structural variation.

  Study EGAS00001000199

• Splenic_Marginal_Zone_Lymphoma_with_villous_lymphocytes_exome_sequencing

  Agilent whole exome hybridisation capture will be performed on genomic DNA derived from ~3 Splenic Marginal Zone Lymphoma with villous lymphocytes samples and matched normal DNA from the same patients. Samples will be multiplexed in one lane of Illumina HiSeq. Sequencing to a coverage of at least 30x will be performed and mapped to build 37 of the human reference genome to facilitate the identification of novel cancer genes.

  Study EGAS00001000139

• Cell_Line_Sub_Clone_Rearrangement_Screen

  Genomic libraries (500 bps) will be generated from total genomic DNA cancer samples and subjected to paired end sequencing on the llumina GA. Paired reads will be mapped to build 37 of the human reference genome to facilitate the generation of genome wide copy number information, and the identification of novel rearranged cancer genes and gene fusions.

  Study EGAS00001000178

• Chordoma_Exome_Sequencing

  Agilent whole exome hybridisation capture will be performed on genomic DNA derived from Chordoma cancers and matched normal DNA from the same patients. Three lanes of Illumina GA sequencing will be performed on the resulting exome libraries and mapped to build 37 of the human reference genome to facilitate the identification of novel cancer genes.

  Study EGAS00001000188

• ADCC_Exome_Sequencing

  Agilent whole exome hybridisation capture will be performed on genomic DNA derived from Adenoid cystic carcinomas and matched normal DNA from the same patients. Three lanes of Illumina GA sequencing will be performed on the resulting exome libraries and mapped to build 37 of the human reference genome to facilitate the identification of novel cancer genes.

  Study EGAS00001000193

• A Comprehensive Catalogue of Somatic Mutations from a Human Cancer Genome

  Study EGAS00001000245

• Genetic landscape of pediatric Infant Acute Lymphoblastic leukemia

  We performed whole genome sequencing of tumor and normal DNA samples obtained from 22 infant ALL cases with MLL rearrangements. In addition, we sequenced 2 paired diagnostic-relapse samples. Using complementary pipelines, somatically acquired genetic changes were analyzed, including single nucleotide variations (SNVs), insertion/deletions, structural variations and copy number variations in the cancer genomes. In addition, exome sequencing was performed on paired diagnostic and normal DNA samples obtained from 20 cases of non-infant MLL rearranged leukemias and somatic mutations in the coding regions were identified.

  Study EGAS00001000246

• AML_targeted_resequencing_study

  Genomic libraries will be generated from whole genome amplified genomic DNA derived from 3,000 myeloid neoplasms. Targeted capture will be performed by multiplexing 16 barcoded samples in each library. Pools of 96 DNA samples will be subjected to 1-2 lanes of HiSeq 75bp sequencing. Reads will be mapped to the current build of the human reference genome to facilitate the generation of a comprehensive catalog of somatic mutations associated with 116 known myeloid and cancer driver genes.

  Study EGAS00001000275

• Pancreatic Cancer Sequencing Initiative

  Pancreatic Cancer Sequencing Initiative for the International Cancer Genome Consortium at the Ontario Institute for Cancer Research.

  Study EGAS00001000343

• Triple_Negative_Breast_Cancer_Whole_Genome_Validations

  We propose to definitively characterise the somatic genetics of Triple negative breast cancer through generation of comprehensive catalogues of somatic mutations in 500 cases by high coverage genome sequencing coupled with integrated transcriptomic and methylation analyses. This study will use a bespoke bait set to pulldown regions of interest found in whole genome sequencing to validate mutations found.

  Study EGAS00001000426

• ERG ALTERATIONS DEFINE A NOVEL SUBTYPE OF ACUTE LYMPHOBLASTIC LEUKEMIA

  Structural chromosomal alterations are a hallmark of acute lymphoblastic leukemia (ALL) yet many patients lack an identifiable abnormality on conventional cytogenetic analysis. Here, using integrated analysis of genome-wide DNA copy number and gene expression data of 1764 childhood and adult ALL cases, including whole-genome, exome and mRNA-sequencing of 72 cases, we report a novel subtype of B-progenitor ALL (B-ALL) representing 4-13% of B-ALL cases characterized by a distinct gene expression profile, and focal deletions of ERG (ETS related gene) in 56% of cases. These cases are characterized by expression of a ERG transcript that utilizes a novel exon in intron 6 of ERG spliced to the canonical reading frame of ERG exons 7-10, encoding a 27 kDa C-terminal ERG protein that retains the ETS and transactivating domains but lacks the N-terminal pointed and regulatory domains. This protein is a competitive inhibitor of wild-type ERG and is leukemogenic in vivo. ERG-altered ALL cases have a favourable outcome despite the presence of alterations associated with poor prognosis in non-ERG ALL, such as deletions of IKZF1. These findings identify a new subtype of leukemia characterized by a novel mechanism of ETS transcription factor dysregulation in cancer.

  Study EGAS00001000514

• Targeted_sequencing_of_genes_recurrently_mutated_in_AML___part2

  Genomic libraries will be generated from total genomic DNA derived from 4000 samples with Acute Myeloid Leukaemia. Libraries will be enriched for a selected panel of genes using a bespoke pulldown protocol. 64 Samples will be individually barcoded and subjected to up to one lanes of Illumina HiSeq. Paired reads will be mapped to build 37 of the human reference genome to facilitate the characterisation of known gene mutations in cancer as well as the validation of potentially novel variants identified by prior exome sequencing.

  Study EGAS00001000570

• Use_of_Deep_Sequencing_to_Dectect_Clonal_Mutations_In_Sun_Exposed_Skin_Epidermis_PART2

  This study aims to define the landscape of somatic mutations in sun exposed human skin by deep sequencing, analyse their frequency and use the data to infer the effect of mutations on proliferating cell behaviour. The frequency of each mutation will reflect the size of the clone of cells in the tissue sample. By analyzing small samples, clones with as few as 100 cells will be detectable. Allele frequency distributions for each mutation will be used to infer cell fate using published methods (Klein et al. 2010). This study will shed unprecedented light on the early clonal events that lead to the emergence of cancer.

  Study EGAS00001000603

• Mosaic_Colorectal_Metastasis

  A comparison of the somatic variation present in a primary colorectal tumour and three different liver metastases from the same patient.

  Study EGAS00001000613

• BIG_MS_Pilot

  Testing logistics and infrastructure of molecular screening program. Core biopsies taken from invasive recurrent or metastatic breast cancer to evaluate and identify molecular traits rendering them suitable for clinical trials

  Study EGAS00001000616

• FinHer_Breast_Cancer_Study

  The purpose of this study is to sequence 500 known cancer genes in 960 newly diagnosed high risk breast cancer patients treated with current standard of care therapies and trastuzumab, for somatic alteration and copy number changes. We will be using next gen sequencing technology to determine the prognostic relevance of these somatic genetic alterations and of teh low frequency events to determine if they are associated with trastuzumab benefit or HER2 positive breast cancer, i.e. treatment interaction. The samples will be analysed adn correlated with clinical variables including outcome.

  Study EGAS00001000648

• High-throughput Detection of Clinically Relevant Mutations in Archived Tumor Samples By Multiplexed PCR and Next Generation Sequencing

  PURPOSE: Tailoring cancer treatment to tumor molecular characteristics promises to make personalized medicine a reality. However, reliable genetic profiling of archived clinical specimens has been hindered by limited sensitivity and high false positive rates. Here, we describe a novel methodology, MMP-seq, which enables sensitive and specific high-throughput, high content genetic profiling in archived clinical samples. EXPERIMENTAL DESIGN: We first validated MMP-seq’s technical performance in 66 cancer cell lines and a Latin square cross-dilution of known somatic mutations. We next characterized the performance of MMP-seq in 17 formalin-fixed paraffin embedded (FFPE) clinical samples using matched fresh frozen (FF) tissue from the same tumors as benchmarks. To demonstrate the potential clinical utility of our methodology, we profiled FFPE tumor samples from 73 endometrial cancer patients. RESULTS: We demonstrated that MMP-seq enabled rapid and simultaneous profiling of a panel of 88 cancer genes in 48 samples, and detected variants at frequencies as low as 0.4%. We identified DNA degradation and deamination as the main error sources and developed practical and robust strategies for mitigating these issues, and dramatically reduced the false positive rate. Applying MMP-seq to a cohort of endometrial tumor samples identified extensive, potentially actionable alterations in the PI3K and RAS pathways, including novel PIK3R1 hotspot mutations that may disrupt negative regulation of PIK3CA. CONCLUSIONS: MMP-seq provides a robust solution for comprehensive, reliable and high- throughput genetic profiling of clinical tumor samples, paving the way for the incorporation of genomic-based testing into clinical investigation and practice.

  Study EGAS00001000674

• Whole Exome Sequencing data of six chRCC tumors corresponding to three patients

  Mammalian target of rapamycin (mTOR) is a central regulator of mammalian metabolism and physiology. Aberrant hyperactivation of the mTOR pathway promotes tumor growth and metastasis, and can also promote tumor resistance to chemotherapy and cancer drugs; this makes mTOR an attractive cancer therapeutic target. mTOR inhibitors have been approved to treat cancer; however, the mechanisms underlying drug sensitivity remain poorly understood. Here, whole exome sequencing of three chromophobe renal cell carcinoma (chRCC) patients with exceptional mTOR inhibitor sensitivity revealed that all three patients shared somatic mutations in the deubiquitinase USP9X. The clonal characteristics of the mutations, which were amassed by studying multiple patients’ primary and metastatic samples from various years, together with the low USP9X mutation rate in unselected chRCC series, reinforced a causal link between USP9X and mTOR inhibitor sensitivity. Rapamycin treatment of USP9X-depleted HeLa and renal cancer 786-O cells, along with the pharmacological inhibition of USP9X, confirmed that this protein plays a role in patients’ sensitivity to mTOR inhibition. USP9X was not found to exert a direct effect on mTORC1, but subsequent ubiquitylome analyses identified p62 as a direct USP9X target. Increased p62 ubiquitination and the augmented rapamycin effect upon bortezomib treatment, together with the results of p62 and LC3 immunofluorescence assays, suggested that dysregulated autophagy in USP9X-depleted cells can have a synergistic effect with mTOR inhibitors. In summary, we show that USP9X constitutes a potential novel marker of sensitivity to mTOR inhibitors in chRCC patients, and represents a clinical strategy for increasing the sensitivity to these drugs.

  Study EGAS00001007104

• HGSOC organoid sequencing study

  Study EGAS00001007189

• BC Cancer, part of the Provincial Health Services Authority, Technology Development Office, Data Access Committee (PHSA TDO DAC)

  Access to data generated by BCCA is made available by completing the data access agreement for review by the data access committee and will be granted to qualified investigators for appropriate use.

  Dac EGAC00000000011

• IRCCS Istituto Romagnolo per lo Studio dei Tumori "Dino Amadori" Italian Cancer Center Data Access Committee

  Dac EGAC00001003227

• SMC Breast Cancer DAC

  Dac EGAC00001002381

• IRCCS Istituto Romagnolo per lo Studio dei Tumori "Dino Amadori" Italian Cancer Center Data Access Committee

  Dac EGAC00001003223

• Somatic mutation rates scale with lifespan across mammals

  The rates and patterns of somatic mutation in normal tissues are largely unknown outside of humans. Comparative analyses can shed light on the diversity of mutagenesis across species and on long-standing hypotheses regarding the evolution of somatic mutation rates and their role in cancer and ageing. Here, we used whole-genome sequencing of 208 intestinal crypts from 56 individuals to study the landscape of somatic mutation across 16 mammalian species. We found somatic mutagenesis to be dominated by seemingly endogenous mutational processes in all species, including 5-methylcytosine deamination and oxidative damage. With some differences, mutational signatures in other species resembled those described in humans, although the relative contribution of each signature varied across species. Remarkably, the somatic mutation rate per year varied greatly across species and exhibited a strong inverse relationship with species lifespan, with no other life-history trait studied displaying a comparable association. Despite widely different life histories among the species surveyed, including ~30-fold variation in lifespan and ~40,000-fold variation in body mass, the somatic mutation burden at the end of lifespan varied only by a factor of ~3. These data unveil common mutational processes across mammals and suggest that somatic mutation rates are evolutionarily constrained and may be a determinant of lifespan.

  Dataset EGAD00001008032

• WGS of peripheral blood leukocytes from patients with Li-Fraumeni syndrome

  We performed whole genome sequencing on 84 LFS family members from 47 families: 22 with wildtype TP53 and 62 with variant TP53. The variant TP53 cohort consists of 49 individuals who developed cancer and 13 individuals who remain cancer-free; 34 were from 13 families with 2-4 individuals sequenced within a given family and the remaining 28 had no family members sequenced. The wildtype cohort consists of 14 individuals who developed cancer and 8 individuals who are cancer-free, from 6 families.

  Dataset EGAD00001010200

• Mult-omics Palbociclib Resistance Study in HR+/HER2– Metastatic Breast Cancer

  This study is multi-omics study of a Asian longitudinal metastatic breast cancer (MBC) cohort treated with palbociclib plus endocrine therapy. It contains NGS of baseline (BL) and progressive disease (PD) from 70 patients, consisting of 79 tumor/normal matched whole exome sequencing (WES) from 62 patients and 90 tumor whole transcriptome sequecing samples (WTS) from 70 patients. There were 56 BL biopsies profiled by WES and 64 by WTS; 23 PD biopsies were profiled by WES and 26 by WTS. Twenty and 23 patients had paired BL and PD biopsies profiled by WES and WTS, respectively.

  Dataset EGAD00001008314

• Transcriptomic analyses of a large cohort of adult B cell acute lyphoblastic leukemia

  Total mononuclear cells (MNC) were isolated from peripheral blood (PB) or bone marrow (BM) samples of 105 Ph-/-/- (B-cell acute lymphoblastic leukemia [B-ALL] triple negative) and 31 Ph+ B-ALL adult patients using Lymphosep (Biowest, Nuaillé, France). A total of 15 samples from healthy subjects were processed including hematopoietic stem-progenitor cells (CD34+) from bone marrow specimens (n = 3), and bone marrow mononuclear cell samples (n = 3) from STEMCELL Technologies (Vancouver, Canada). PB MNC samples (n=5) and cord blood samples (n = 4). CD34+ cells were enriched from cord blood samples by immunomagnetic separation (CD34 MicroBead Kit, Miltenyi Biotec, Bergisch Gladbach, Germany).Libraries were prepared using the TruSight RNA Pan-Cancer Panel Kit (Illumina, San Diego, California, USA), following the manufacturer’s protocol. Sequencing was performed using the Illumina MiSeq instrument.

  Dataset EGAD00001010837

• Serum Proteome Profiling Identifies Early Markers of Therapeutic Response to Neoadjuvant Chemotherapy of Breast Cancer

  We performed a proteomic serum profiling of patients with non-metastasized breast cancer (BC) who received neoadjuvant chemotherapy (NACT). Samples were collected at three timepoints during NACT. Furthermore, we compared serum samples of BC patients pre-NACT to a control group of healthy volunteers.

  Dataset EGAD00010002330

• WGS

  Whole-genome sequencing of pancreatic cancer organoids and matched germline controls.

  Dataset EGAD00001010835

• WGS

  Whole-genome sequencing of pancreatic cancer organoids and matched germline controls.

  Study EGAS00001007211

• Digital tEchnology For Lung Cancer Treatment

  The aim of the DEFLeCT project (Digital tEchnology For Lung Cancer Treatment) is to generate a technological platform for precision medicine in order to set predictive personalised algorithms for patient diagnosis and therapy. All resectable patients having histologically confirmed stage IB-IIIA non-small cell lung cancer(NSCLC) will be enrolled in the PROMOLE study, a related and ongoing observational prospective clinical study, for tissue sampling. A large biobank of lung cancer samples and the corresponding healthy tissues and biological components (ie, blood, stools, etc.) with complete clinical, pathological and molecular information will be collected. The project will lay the basis of a knowledge hub and qualified technology aimed not only at answering the medical and scientific community's questions, but also meant to be useful to individual patients by predicting the response to adjuvant and second-line drugs in case of relapse of the disease.

  Study EGAS00001007219

• RNAseq

  RNAseq of pancreatic cancer organoids.

  Dataset EGAD00001010834

• Digital tEchnology For Lung Cancer Treatment

  DEFLeCT metadata: 1) A table containing the mutational profile for all human genes across the cohort of the 81 PROMOLE lung cancer samples. 2) A table containing the expression levels for all human genes across the cohort of the 81 PROMOLE lung cancer samples. 3) A table containing the clinical, histology data and follow-ups of the cohort of 81 PROMOLE lung cancer patients.

  Dataset EGAD00001010838

• RNAseq of GEPARSIXTO

  294 formalin-fixed paraffin-embedded (FFPE) tissue samples were sent to the UNC Lineberger Comprehensive Cancer Center Translational Genomics Lab (TGL) for RNA isolation using the Maxwell 16 MDx Instrument (Promega AS3000) and the Maxwell 16 LEV RNA FFPE Kit (Promega AS1260) following the manufacturer’s protocol (Promega 9FB167). 279 total RNA sequencing libraries were prepared at TGL using a Bravo Automated Liquid-Handling Platform (Agilent G5562A) and the TruSeq Stranded Total RNA Library Prep Gold Kit (Illumina 20020599) following the manufacturer’s protocol (Illumina 1000000040499). RNAseq library quality and quantity were measured using a TapeStation 4200 (Agilent G2991AA) and Qubit 3.0 fluorometer (Life Technologies Q33216), pooled at equal molar ratios, and denatured following the manufacturer’s protocol (Illumina 1000000106351). 271 total RNA sequencing libraries were sequenced at TGL on NovaSeq 6000 (Illumina 20012850) S4 flow cells (Illumina 20028313) following the manufacturer’s protocol (Illumina 1000000019358) using a 2x50 bp paired-end configuration and pool sizes of 91 libraries to target a read depth of 110 million clusters per library on average.

  Dataset EGAD00001010201

• Sequence of breast cancer bone metastases PDX from 2 targeted panels

  Sequence of breast cancer bone metastases PDX obtained by 2 targeted panels

  Dataset EGAD00001010856

• Sequence of breast cancer bone metastases PDX from 2 targeted panels

  Sequence of breast cancer bone metastases PDX obtained by 2 targeted panels

  Dataset EGAD00001010860

• SNP data for Breast cancer PRS

  SNP data for 313 loci required for calculation of the Breast cancer PRS

  Dataset EGAD00001008144

• SNP data for Ovarian cancer PRS (controls)

  SNP data of 28 sites required for the Ovarian cancer PRS (controls)

  Dataset EGAD00001008145

• Methylation profiles in blood (breast cancer cases)

  Raw methylation data from blood samples in breast cancer cases.

  Dataset EGAD00010002470

• Breast cancer bone metastases

  Dac EGAC00001003238

• RRBS data from TRACERx non-small cell lung cancer (NSCLC) tumours and matched normal adjacent tissue.

  TRACERx (TRAcking Cancer Evolution through therapy (Rx)) is a prospective cohort study designed to investigate intratumor heterogeneity (ITH) in relation to clinical outcome, and to determine the clonal nature of driver events and evolutionary processes in early stage non-small cell lung cancer (NSCLC). This study looks at multi-region RRBS data from the TRACERx cohort selected for quantity of material available and high tumour purity

  Study EGAS00001006523

• TRACERx Reduced-representation bisulfite sequencing (RRBS)

  RRBS data from TRACERx non-small cell lung cancer (NSCLC) tumours and matched normal adjacent tissue. TRACERx (TRAcking Cancer Evolution through therapy (Rx)) is a prospective cohort study designed to investigate intratumor heterogeneity (ITH) in relation to clinical outcome, and to determine the clonal nature of driver events and evolutionary processes in early stage non-small cell lung cancer (NSCLC).

  Dataset EGAD00001009707

• Melanoma PEACE Dataset

  Dataset for the initial melanoma PEACE paper in Cancer Discovery, March 2023.

  Dataset EGAD00001010285

• Genomic Landscape of Follicular Lymphoma Across a Wide Spectrum of Clinical Behaviors

  Study EGAS00001007105

• Lung Cancer Single-cell Data Access Committee

  Dac EGAC00001001220

• CRISPR transduction of iPS cells

  Genome engineering using CRISPR/Cas9 technology enables simple, efficient and precise genomic modifications in human cells. Conventional immortalized cell lines can be easily edited or screened using genome-wide libraries with lentiviral transduction. However, cell types derived from the differentiation of induced Pluripotent Stem Cells (iPSC), which often represent more relevant, patient-derived models for human pathology, are much more difficult to engineer as CRISPR/Cas9 delivery to these differentiated cells can be inefficient and toxic. Here, we present an efficient, lentiviral transduction protocol for delivery of CRISPR/Cas9 to macrophages derived from human iPSC with efficiencies close to 100%. We demonstrate CRISPR/Cas9 knockouts for three non-essential proof-of-concept genes - HPRT1, PPIB and CDK4. We then scale the protocol and validate for a genome-wide pooled CRISPR/Cas9 loss-of-function screen. This methodology enables, for the first time, systematic exploration of macrophage involvement in immune responses, chronic inflammation, neurodegenerative diseases and cancer progression, using efficient genome editing techniques.

  Study EGAS00001005102

• Somatic mutations in facial skin from countries of contrasting skin cancer risk

  The incidence of non-melanoma skin cancer is 17-fold lower in Singapore compared to the UK1, despite Singapore receiving 2-3 times more year-round ultraviolet radiation (UV)2,3. The ageing epidermis of the skin comprises competing somatic mutant clones4,5, from which such cancers develop. We question if differences in keratinocyte skin cancer incidence are reflected in the mutational landscape by comparing ageing facial epidermis from donors of Singapore and the UK. We find UK skin to be a highly competitive, densely mutated landscape with 4-fold greater mutation burden compared to Singaporean skin and differences in clonal selection by country. We disproportionately observe multiple features common to keratinocyte skin cancers6,7,8 in UK skin, such as UV mutagenesis, copy number aberration and hotspot mutations (in particular TP53 R248W). We conclude that keratinocyte skin cancer incidence is reflected in the somatic clones of non-cancerous epidermis. Finally, we re-analyse squamous cell carcinoma exomes from Korea9 to show, even in low incidence populations, carcinogenesis is driven by UV damage.

  Dataset EGAD00001009666

• Processed bam files for the whole exome sequencing of primary lung adenocarcinoma samples

  We performed single cell RNA sequencing (scRNA-seq) for 208,506 cells derived from 58 lung adenocarcinomas from 44 patients, which covers primary tumour, lymph node and brain metastases, and pleural effusion in addition to normal lung tissues and lymph nodes. The extensive single cell profiles depicted a complex cellular atlas and dynamics during lung adenocarcinoma progression which includes cancer, stromal, and immune cells in the surrounding tumor microenvironments.

  Dataset EGAD00001010320

• Data Access Committee for data from EGAS00001002864: Genome analysis of oesophageal cancer and Barretts oesophagus

  Dac EGAC00001000863

• Molecular_risk_stratification_in_patients_with_T1_colorectal_cancer_WES

  The introduction of bowel cancer screening has led to a significant increase in the proportion of patients being diagnosed with asymptomatic, early-stage colorectal cancer (CRC). Although the majority of these patients are successfully treated with surgery alone, a small proportion of patients have ‘born-to-be-bad’ aggressive lesions with early dissemination leading to distant metastases. Current standard of care histological assessment is unable to distinguish between these aggressive versus non-aggressive early lesions which is essential to provide appropriate clinical management decisions. This study aims to carry out molecular and histological profiling of approximately 300 T1 CRCs in order to develop a molecular stratifier based on the risk of relapse in early-invasive CRC. This novel T1 cohort will represent the world’s largest molecularly characterised T1 cohort of samples, with digital pathology assessment alongside whole exome sequencing, copy number variation analysis and 3’ RNA-seq. This data will be used to generate a robust panel of molecular and/or histological markers applicable to formalin-fixed paraffin embedded (FFPE) archival tissue which discriminates between T1 lesions based on risk of relapse, which will ultimately be used to inform clinical management of CRC at the earliest stages of the disease.

  Study EGAS00001005734

• Treatment stratification and biomarker validation using patient-derived head and neck cancer organoids

  Background Organoids are three-dimensional structures that can be grown from patient-derived material including carcinomas. These in vitro models can be cryopreserved to generate “living” biobanks that reflect patient heterogeneity. Head and neck cancer (HNC) is a collective term used for tumors arising in the head and neck area, including squamous cell carcinomas (HNSCC) and adenocarcinoma of the salivary gland. Methods to culture patient-derived HNC organoids have previously been described. Methods Organoids were derived from resection or biopsy material of patients included between 2016 and 2022. Organoids were characterised with immunohistochemistry and whole exome sequencing (WES) and exposed to chemo-, radio- and targeted-therapies. CRISPR/Cas9-based gene editing was applied to validate proposed biomarkers. Results We have extended our previously published organoid biobank to a total of 110 organoid models, some of which were characterised by histology and WES. Organoids recapitulated both single nucleotide variants and copy number alterations as found in patient HNSCC samples. Organoid and patient response to radiotherapy (RT; primary (n=6) and adjuvant (n=15)) could be compared in 21 HNC cases. In the adjuvant RT group, organoids derived from patients that relapsed were more resistant to RT in vitro, showing potential for guiding treatment options in this subset of patients. Conclusion Taken together, these results indicate illustrate the potential of organoids as a diagnostic tool in personalised medicine for HNC and indicate the potential of this technology for biomarker discovery and validation within the context of relevant patient heterogeneity.

  Study EGAS00001007076

• Whole genome sequencing data of high-grade serous ovarian cancer samples (set 4)

  Whole genome sequencing data of 7 high-grade serous carcinoma (HGSC) patients (32 samples) sequenced with HiSeq X Ten.

  Dataset EGAD00001010066

• patient-derived head and neck cancer organoids

  patient-derived head and neck cancer organoids

  Dataset EGAD00001010134

• Whole exome and RNA sequencing data from urothelial bladder cancer patients treated with anti-PD-(L)1

  We have generated and analyzed genomic data from a cohort of metastatic urothelial carcinoma patients treated with ICI such as anti-PD-(L)1 monoclonal antibodies. The dataset contains whole exome sequencing data of 27 whole blood samples and 27 FFPE tumor samples. Further, it includes RNA sequencing data from 21 tumor samples. Following the RECIST criteria, 10 patients were classified as non-responders to the treatment, and 17 were responders. The dataset also contains a merged vcf file containing somatic mutations called by Strelka2 and Mutect2 following the gatk best practice pipeline.

  Dataset EGAD00001010324

• Whole genome sequencing data of high-grade serous ovarian cancer samples (set 6)

  Whole genome sequencing data of 31 high-grade serous carcinoma (HGSC) patients (101 samples) sequenced with HiSeq X Ten and BGISEQ-500

  Dataset EGAD00001010202

• The dataset for Single molecule genome-wide mutation profiles of cell-free DNA for non-invasive detection of cancer

  The dataset for Single molecule genome-wide mutation profiles of cell-free DNA for non-invasive detection of cancer includes 57 BAM files from whole genome next-generation sequencing on the Illumina HiSeq2500. The samples analyzed include plasma samples from individuals with and without cancer.

  Dataset EGAD00001010891

• BC Cancer, part of the Provincial Health Services Authority, Technology Development Office, Data Access Committee (PHSA TDO DAC)

  Dac EGAC00001003254

• Submission 80 - study_title 1

  Submission 80 - description 1

  Study EGAS50000000118

• Novel mutations in TOP2A in gliomas

  High grade gliomas (HGGs) are aggressive, primary brain tumors with poor clinical outcomes. To better understand glioma pathobiology and find potential therapeutic susceptibilities, we designed a custom- panel 664 cancer- and epigenetics-related genes and employed targeted next generation sequencing to study the genomic landscape of somatic and germline variants in 182 glioma samples of different malignancy grades. Besides known alterations in TP53, IDH1, ATRX, EGFR genes, we found several novel variants that can be potential drivers in gliomas. In four patients from the Polish glioma cohort, we identified a novel recurrent mutation in the TOP2A gene coding for Topoisomerase 2A in glioblastomas (GBM, WHO grade IV gliomas). The mutation results in a substitution of glutamic acid (E) 948 to glutamine (Q) of TOP2 A and we predicted this E948Q substitution may affect DNA binding and a TOP2A enzymatic activity.

  Study EGAS00001004556

• Clinical outcomes and immune correlates of response to nivolumab plus chemoradiotherapy in women with locally-advanced cervical cancer – NiCOL study

  Concurrent chemoradiotherapy (CRT) with blockade of the PD-1 pathway may enhance immune-mediated tumor control through increased phagocytosis, cell death, and antigen presentation. The NiCOL phase 1 trial was designed to determine safety, tolerance, and immune correlates of response to the PD-1 blocking antibody, nivolumab, with and following concurrent CRT in 16 women with locally advanced cervical cancer (LACC). Three patients experienced grade 3 dose-limiting toxicities. The overall response rate was 93.8% [95%CI: 69.8%-99.8%] with a 2-year PFS of 75% [95% CI: 56.5%-99.5%]. Compared to patients with progressive disease (PD), progression-free (PF) subjects showed a brisker stromal immune infiltrate, higher proximity of tumor-infiltrating CD3+ T cells to PD-L1+ tumor cells and of Foxp3+ T cells to proliferating CD11c+ myeloid cells. PF had higher baseline levels of PD-1 on EMRA CD4+ T cells and ICOS-L on tumor-associated macrophages (TAMs) vs PD, which instead displayed enhanced PD-L1 expression on TAMs and higher, circulating frequencies of proliferating Tregs at baseline. Concomitant nivolumab plus definitive CRT is safe and associated with encouraging PFS rates. Further validation in the subset of LACC displaying pre-existing, adaptive immune activation is warranted.

  Study EGAS00001007297

• Genomic and transcriptomic data of glioma specimens

  Dataset consists of 207 glioma samples of WHO grades II, III and IV. Dataset consists 182 tumor derived genomic data of ~700 cancer-related and epigenetic-related genes with matched blood samples for 48 specimens. Dataset also consists transcriptomic data for 105 specimens. In total 335 bam files were deposited.

  Dataset EGAD00001006299