5731 results for "canc*"

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• Discrepancies in Tumour Mutation Burden (TMB) reporting from sequential Endobronchial ultrasound trans bronchial needle aspiration (EBUS TBNA) samples within single lymph node stations

  Introduction: Tumour Mutation Burden (TMB) is a potential biomarker for immune therapies. Identifying factors that may affect TMB prediction is key to its utility as biomarker for treatment options. Here we investigated parameters that might affect TMB using cytology smears obtained from endobronchial ultrasound transbronchial needle aspiration (EBUS TBNA)-sampled malignant lymph nodes, which are often the only diagnostic samples collected in patients with advanced lung cancer. Methods: Individual Diff-Quik cytology smears were prepared for each needle pass from the same enlarged malignant mediastinal lymph nodes. DNA extracted from smears of each pass underwent sequencing using a large gene panel sequencing (TSO500, Illumina). TMB was estimated for each individual needle pass using the TSO500 Local App v. 2.0 (Illumina). Results: Twenty patients had two or more Diff-Quik smears (total 45 smears) which passed sequencing quality control. Average TMB for all smears was 8.7 ± 5.0 mutations per megabase (Mb). Sixteen of the 20 patients had paired samples with minimal differences in TMB score (average difference 1.3 ± 0.85). Paired samples from 13 patients had concordant TMB in terms of scores being below or above a threshold of 10 mutations/Mb. Samples from seven patients had discrepant TMB, with four cases in particular exhibiting an average difference of 11.3 ± 2.7 mutations/Mb. Factors affecting TMB calling involved tumour content of the samples, the amount of DNA used in sequencing as well as bone fide intra tumour heterogeneity between paired samples. Conclusions: TMB assessment is feasible from EBUS-TBNA derived Diff-Quik slides from a single needle pass. Repeated samples of one or more lymph nodes have minimal variation in TMB in most cases (80%), suggesting accuracy of the test overall. To enhance accuracy of the result, care should be taken in relation to the tumour content of the cytology smear. Further, clinicians should be aware that even slight differences in lymph node site selection could give rise to variable genomics and discrepant TMB due to tumour heterogeneity. Therefore, it would be reasonable for multi-lymph node site analysis of TMB to be performed using EBUS TBNA aspirates from different easily accessible lymph nodes. Further investigations need to determine whether these samples should be combined as one sample or tested separately.

  Study EGAS00001007484

• Exome_sequencing_of_EBV_driven_lymphoma

  Exome sequencing of a case of lethal EBV-driven LPD

  Study EGAS00001001021

• Genomic Alterations in Gingivo-buccal Cancer: ICGC-India Project_YR02

  As a part of the ICGC, India has undertaken genomic studies on gingivobuccal cancer of the oral cavity, which is the most prevalent form of cancer among men in India. There are various known environmental (life-style) correlates of this cancer, the most important of which are tobacco chewing and HPV infection. Paired DNA samples – isolated from the tumour tissue and from the blood of fifty six patients – have been analyzed to catalog germline and somatic mutations. Association between each observed genomic alteration and exposure to environmental risk factors is being explored.Detailed clinical characterization of the patients, collection of data on demographic and environmental exposures, and isolation of DNA samples from blood and tumour tissues collected from each patient are being done at the Advanced Centre for Research, Treatment and Education on Cancer, Mumbai. Exome capture and deep resequencing are being performed at the National Institute of Biomedical Genomics, Kalyani. We have analyzed the exomes of paired blood and tumour DNA samples using exome capture by Illumina TrueSeq Exome Enrichment kit followed by sequencing on Illumina HiSeq-2000. Each exome is being sequenced at a mean depth of 70x for Tumour and 40x for Blood. In addition, we have used Illumina Omni 2.5 SNP-chips to generate genotype data.

  Study EGAS00001001028

• Single-cell RNA sequencing of 22 Hodgkin lymphoma tumors and 5 reactive lymph nodes

  Hodgkin lymphoma (HL) is characterized by an extensively dominant tumor microenvironment (TME) composed of different types of non-cancerous immune cells with rare malignant cells. Characterization of the cellular components and their spatial relationship is crucial to understanding crosstalk and therapeutic targeting in the TME. We performed single-cell RNA sequencing of more than 127,000 cells from 22 HL tissue specimens and 5 reactive lymph nodes, profiling for the first time the phenotype of the HL-specific immune microenvironment at single-cell resolution. Library preparation was performed using the 10x Genomics Chromium system, and Illumina sequencing was used to generate 3' gene expression data for every cell. Downstream analysis was performed in R to identify HL-specific microenvironment patterns and identify novel cell populations.

  Study EGAS00001004085

• Barcelona_kids_with_melanoma

  This set of samples is composed of eight young people (7-16 years old) that have developed melanoma with first-degree relatives that have also developed cancer, which suggests a genetic component to their disease. Here we want to sequence these samples in order to find the causative mutations. As these samples do not carry any of the high-penetrance mutations known to date, finding the genes(s) responsible will offer new insights into the genetic mechanisms underlying predisposition to melanoma.

  Study EGAS00001000733

• 54 metastatic colorectal cancer patients from Schleswig-Holstein in North Germany

  Personalized treatment vs standard of care is much debated, especially in clinical practice. Here we investigated whether overall survival differences in metastatic colorectal cancer patients are explained by their tumor mutation profiles or by their treatment differences in real clinical practice.

  Study EGAS00001004108

• GIST_SSGXVIII_trial_targeted_gene_sequencing

  Targeted cancer gene sequencing of samples enrolled in the SSGXVIII trial from Finland.

  Study EGAS00001001054

• Exome-seq, RNA-Seq, SNP array profiling of gastric tumor samples and cell lines.

  Gastric cancer is the second leading cause of worldwide cancer mortality, yet the underlying genomic alterations remain poorly understood. Here we performed exome and transcriptome sequencing and SNP array assays to characterize 51 primary gastric tumors and 32 cell lines. Meta-analysis of the exome data and previously published data sets revealed 24 significantly mutated genes in MSS tumors, and 16 in MSI tumors. More than half of the patients in our collection could potentially benefit from targeted therapies. We identified 55 splice-site mutations accompanied by aberrant splicing products, in addition to mutation-independent differential isoform usage in tumors. The ZAK kinase isoform TV1 is preferentially upregulated in gastric tumors and cell lines relative to normal samples. This pattern is also observed in colorectal, bladder, and breast cancers. Overexpression of this particular isoform activated multiple cancer-related transcription factor reporters, while depletion of ZAK in gastric cell lines inhibited proliferation. These results reveal the spectrum of genomic and transcriptomic alterations in gastric cancer, and identify isoform-specific oncogenic properties of ZAK.

  Study EGAS00001000736

• Cell_lines_with_telomere_fusion_induced_rearrangements

  Whole-genome somatic rearrangement and point mutation analysis in cell lines with induced telomere fusions.

  Study EGAS00001001059

• CRISPR_screen_M14__NCI_H3122

  Genome wide CRISPR screen was performed to find resistance to targeted drugs for melanoma and lung

  Study EGAS00001001060

• ESGI_Exome_sequencing_in_Circulating_Tumor_Cells_to_determine_therapy_related_markers_____

  The objectives of this project are the identification of markers related to cancer therapy resistance in the blood of breast cancer patients and to study the genetic changes in cancer cells during this development of resistance. Whole genome amplified DNA from Circulating Tumor Cells (CTCs), selected during the course of systemic treatment from blood of metastatic breast cancer patients, will be exome sequenced . The patients selected for this study did not respond to therapy.

  Study EGAS00001000747

• RNAseq data to study PRPF6 regulated splice forms in colon cancer cell lines

  Alternative splicing plays critical roles in differentiation, development, and cancer (Pettigrew et al., 2008; Chen and Manley, 2009). The recent identification of specific spliceosome inhibitors has generated interest in the therapeutic potential of targeting this cellular process (van Alphen et al., 2009). Using an integrated genomic approach, we have identified PRPF6, an RNA binding component of the pre-mRNA spliceosome, as an essential driver of oncogenesis in colon cancer. Importantly, PRPF6 is both amplified and overexpressed in colon cancer, and only colon cancer cells with high PRPF6 levels are sensitive to its loss. Our data clearly point to an important role for PRPF6 in colon cancer growth and suggest that a better understanding of its role in alternative splicing in colon cancer is warranted. To determine the specific alternative splice forms that PRPF6 regulates in colon cancer, we plan three experiments: 1. The first involves knocking down expression of PRPF6 in two different cancer cell lines with 3 different siRNAs, and then completing RNA-seq to determine the gene expression changes that occur relative to a non-targeting control siRNA. Because of the role for PRPF6 in pre-mRNA splicing, we especially want to quantify the changes in splice-specific forms of all genes genome-wide to identify genes whose splicing is altered upon PRPF6 knockdown. 2. The second involves immunoprecipitating PRPF6 from two different cancer cell lines and isolating any RNA that is bound to PRPF6, since PRPF6 is an RNA-binding protein. We then want to carry out RNA-seq to identify which RNA molecules co-immunoprecipitated with PRPF6. This will help us determine possible functions for PRPF6 in regulating colon cancer growth. 3. The third involves overexpressing PRPF6 in cell lines and then carrying out RNA-seq to identify any changes in splice-specific gene expression. This will allow us to determine whether increased PRPF6 expression is sufficient to drive alternative splicing changes.

  Study EGAS00001000761

• MYD88/TLR mutations in CLL

  The Chronic Lymphocytic Leukemia (CLL) Genome Project aims to identify genetic alterations involved in the development and progression of the CLL, which are still unknown, with the objective of generating a comprehensive catalogue of genetic alterations in 500 independent tumours. The CLL Genome Project, as a contributing member of the International Cancer Genome Consortium (ICGC), has the purposes of creating diagnostic tools, discovering therapeutic targets and developing new strategies that will allow a customized therapy for CLL in order to make it more precise and effective.

  Study EGAS00001000772

• In_Situ_Transcription_whole_genome_sequencing

  Whole genome sequencing of multifocal breast cancer regions. Intention to use this data to inform in-situ transcription analysis.

  Study EGAS00001001971

• Colorectal_organoids_and_tumour_tissue___Whole_Genome_X10

  Whole genome sequencing of single cell derived organoids from normal colon tissue and colorectal cancer.

  Study EGAS00001001100

• ESGI___Whole_Genome_Sequencing_of_samples_from_the_ORCADES_cohort__X10__

  Deep whole genome sequencing of sampels from the Orkney Complex Disease Study (ORCADES), each with data on up to 300 quantitative traits and other risk factors associated with cardiovascular, metabolic and other complex diseases. The samples are sequenced using the Illumina HiSeq X Ten system.

  Study EGAS00001001125

• Whole genome and RNA sequencing of paediatric glioblastoma in the ICGC PedBrain project

  Paediatric glioblastoma (pedGBM) is characterised by substantial intertumoural heterogeneity. In order to identify the genetic lesions underlying tumourigenesis, we analysed whole genomes and transcriptomes of pedGBMs and in vitro model systems by next generation sequencing. Novel fusions of the receptor tyrosine kinase MET lead us to investigate targeted therapy using MET inhibitors. This study is part of the International Cancer Genome Consortium PedBrain Tumor Project (ICGC PedBrain, http://www.pedbraintumor.org/).

  Study EGAS00001001139

• MutWP1__CRUK_Grand_Challenge_Mutographs_of_Cancer__clear_cell_renal_cell_carcinoma___2

  The Mutographs project aims to advance our understanding of the causes of cancer through studies of mutational signatures. Led by Mike Stratton, together with Paul Brennan, Ludmil Alexandrov, Allan Balmain, David Phillips and Peter Campbell, this large-scale international research endeavour was awarded a Cancer Research UK Grand Challenge. Different patterns of somatic mutation are generated by the different environmental, lifestyle and genetic factors that cause cancer, many of them are still unknown. Within Mutographs, the International Agency for Research on Cancer is coordinating the recruitment of 5000 individuals with cancer (colorectal, renal, pancreatic, oesophageal adenocarcinoma or oesophageal squamous cancers) across 5 continents to explore whether different mutational signatures explain marked variation in incidence. In brief, through an international network of collaborators around the world, biological materials are collected, along with demographic, histological, clinical and questionnaire data. Whole genome sequences of tumour-germline DNA pairs are generated at the Wellcome Trust Sanger Institute. Somatic mutational signatures are subsequently extracted by non-negative matrix factorisation methods and correlated with risk factors data. Through an enhanced understanding of cancer aetiology, Mutographs unprecedented effort is anticipated to outline modifiable risk factors, lead to new approaches to prevent cancer, and provide opportunities to empower early detection, refine high-risk groups and contribute to further therapeutic development.

  Study EGAS00001003542

• LINE_luminal_breast_cancer_Neoadjuvant_Chemotherapy_Study

  A targeted gene screen of 365 known cancer genes in luminal breast cancer samples pre-chemotherapy and at resection post-chemotherapy to evalaute clonal expansion of chemotherapy cancer cells.

  Study EGAS00001001223

• Multiple_Myeloma_Diagnosis_to_Relapse_study_samples

  The study will investigate serial samples from the same patient taken at the time of MGUS or SMM diagnosis, and later at the time of evolution towards MM. Samples will be sequenced by whole genome along with a matched normal to obtain the highest possible amount of information toinvestigate genomic changes at disease evolution.

  Study EGAS00001001299

• Breast_Heterogeneity_Validation

  Validation of subs and indels called in breast whole genome studies

  Study EGAS00001001972

• Pre_clinical_evolution_of_haematological_malignancies

  Deep targeted sequencing of 291 peripheral blood samples taken 1-20 years prior diagnosis of a haematological malignancy alongside age- and sex-matched controls. Key objective is to distinguish indolent age-related clonal haematopoiesis from pre-cancer and to derive predictive models for early risk-stratification.

  Study EGAS00001002964

• Leeds_Melanoma_Cohort

  Leeds Melanoma Cohort

  Study EGAS00001001158

• Anaplastic_Meningioma_V3__cancer_gene_panel

  Investigation into causal genes underlying anaplastic meningioma

  Study EGAS00001001155

• Exploring_the_landscape_of_somatic_mutations_in_normal_tissue___GI___MAP___WGS

  Somatic mutations (burdens and signatures) and clonal dynamics in normal human tissues from the gastrointestinal tract of individuals with tumour predisposition syndromes and DNA damage repair defects.

  Study EGAS00001004122