5735 results for "canc*"

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• WGS of breast cancer diagnosed during pregnancy and matched control

  The aim of this study was to compare the mutational landscape of breast cancer diagnosed during pregnancy (BCP) and breast cancer from age/stage non-pregnant patients (controls). We present whole genome sequencing data (Illumina HiSeq X ten platform) of tumor and matched normal tissues from 35 BCP patients and 20 controls. This work provides important novel biological insights and a unique resource to study the biology of breast cancer in young women and how pregnancy could modulate tumor biology.

  Study EGAS00001002685

• Gut microbiome modulates response to anti PD1 immunotherapy in metastatic melanoma patients

  There is a growing appreciation of the role of the microbiome in cancer, and evidence in pre-clinical models that the gut microbiome may modulate responses to immune checkpoint blockade though this has not been well-characterized in patients. We analyzed the oral (n=86)and gut (n=43) 16S microbiome in melanoma patients on PD-1 blockade. Significant differences were noted in the diversity and composition of the gut microbiome between responders and non-responders in patients with a fecal microbiome sample, with significantly higher alpha diversity and relative abundance of Ruminococcaceae bacteria) in R. Metagenomic studies (n=25) revealed functional differences in gut bacteria in R including enrichment of anabolic pathways. Immune profiling demonstrated enhanced systemic and anti-tumor immunity in patients with a favorable gut microbiome as well as in germ-free mice receiving fecal transplant from responding patients. Together, these data have important implications for treatment with immune checkpoint blockade in cancer. The fastq files associated with this dataset are stored at ENA under the following accession numbers: PRJEB22894 (Fecal 16S), PRJEB22874 (Oral 16S), PRJEB22895 (Murine 16S), PRJEB22893 (Fecal WGS).

  Study EGAS00001002698

• TCR β-chain repertoire characterization of regulatory and conventional T cells in peripheral blood from breast cancer patients and healthy individuals.

  Identification of tumor-specific effects on peripheral TCRβ repertoire formation in humans, investigation of the clonal origin of regulatory T cells in breast cancer patients and impact analysis of the tumor-specific conversion of conventional T cells into induced regulatory T cells on the peripheral Treg repertoire in humans.

  Study EGAS00001002699

• The integrated genomic and immune landscapes of lethal metastatic breast cancer.

  We report on the extensive molecular profiling of multiple individual metastases from 10 warm autopsies of patients with lethal multi-therapy resistant breast cancers.

  Study EGAS00001002703

• Dynamics of neoantigen landscape during immunotherapy

  Immune checkpoint inhibitors have shown significant therapeutic responses against tumors containing increased mutation-associated neoantigen load. We have examined the evolving landscape of tumor neoantigens during the emergence of acquired resistance in non-small cell lung cancer patients after initial response to immune checkpoint blockade with anti-PD1 or anti-PD-1/anti-CTLA4 antibodies. Analyses of matched pretreatment and resistant tumors identified genomic changes resulting in loss of 7 to 18 putative mutation-associated neoantigens in resistant clones. Peptides generated from the eliminated neoantigens elicited clonal T cell expansion in autologous T cell cultures, suggesting that they generated functional immune responses. Neoantigen loss occurred through elimination of tumor subclones or through deletion of chromosomal regions containing truncal alterations and were associated with changes in T cell receptor clonality. These analyses provide insights into the dynamics of mutational landscapes during immune checkpoint blockade and have implications for development of immune therapies that target tumor neoantigens.

  Study EGAS00001002704

• Sequencing-based counting and size profiling of plasma Epstein-Barr virus DNA enhance population screening of nasopharyngeal carcinoma.

  Circulating tumor-derived DNA testing for cancer screening has recently been demonstrated in a prospective study on identification of nasopharyngeal carcinoma (NPC) among 20,174 asymptomatic individuals. Plasma EBV DNA, a marker for NPC, was detected using real-time PCR. While plasma EBV DNA was persistently detectable in 97.1% of the NPCs identified, ∼5% of the general population had transiently detectable plasma EBV DNA. We hypothesized that EBV DNA in plasma of subjects with or without NPC may have different molecular characteristics. We performed target-capture sequencing of plasma EBV DNA and identified differences in the abundance and size profiles of EBV DNA molecules within plasma of NPC and non-NPC subjects. NPC patients had significantly higher amounts of plasma EBV DNA, which showed longer fragment lengths. Cutoff values were established from an exploratory dataset and tested in a validation sample set. Adopting an algorithm that required a sample to concurrently pass cutoffs for EBV DNA counting and size measurements, NPCs were detected at a positive predictive value (PPV) of 19.6%. This represented superior performance compared with the PPV of 11.0% in the prospective screening study, which required participants with an initially detectable plasma EBV DNA result to be retested within 4 weeks. The observed differences in the molecular nature of EBV DNA molecules in plasma of subjects with or without NPC were successfully translated into a sequencing-based test that had a high PPV for NPC screening and achievable through single time-point testing.

  Study EGAS00001002707

• Colorectal adenomas and carcinomas NKI-AvL TGO series Gut2009

  Colorectal cancer (CRC) develops from normal epithelium, through a benign precursor lesion called adenoma, by accumulation of genetic alterations affecting oncogenes and tumour suppressor genes. These CRC-related genomic alterations often result in specific RNA-expression patterns. RNA isolated from fresh frozen specimen of 32 adenomas and 29 CRCs was obtained from the previously published study (Carvalho et al. 2009) and RNA-sequencing was performed with the aim to examine RNA expression changes in colorectal adenoma-to-carcinoma progression.

  Study EGAS00001002758

• The temporal mutational and immune tumour microenvironment remodelling of HER2-negative primary breast cancers

  WES and clonality characterization of different timepoints in HER2-negative primary breast cancers receiving neoadjuvant eribulin therapy.

  Study EGAS00001004953

• Exome array analysis of adverse reactions to fluoropyrimidine-based therapy for gastrointestinal cancer

  Fluoropyrimidines, including 5-fluororacil (5FU) and its pro-drug Capecitabine, are the common treatment for colorectal, breast, neck and head cancers – either as monotherapy or in combination therapy. Adverse reactions (ADRs) to the treatment are common and often result in treatment discontinuation or dose reduction. Factors contributing to ADRs, including genetic variation, are poorly characterized. We performed exome array analysis to identify genetic variants that contribute to adverse reactions.Our final dataset consisted of 504 European ancestry individuals undergoing fluoropyrimidine-based therapy for gastrointestinal cancer. A subset of 254 of these were treated with Capecitabine. All individuals were genotyped on the Illumina HumanExome Array.

  Study EGAS00001002763

• Detection and localization of surgically resectable cancers with a multi-analyte blood test

  Earlier detection is key to reducing cancer deaths. Here we describe a blood test that can detect eight common cancer types through assessment of the levels of circulating proteins and mutations in cell-free DNA. We applied this test, called CancerSEEK, to 1,005 patients with clinically detected cancers of the ovary, liver, stomach, pancreas, esophagus, colorectum, lung, or breast. CancerSEEK tests were positive in a median of 70% of the eight cancer types. The sensitivities ranged from 69% to 98% for the detection of five cancer types (ovary, liver, stomach, pancreas, and esophagus) for which there are no screening tests available for average-risk individuals. The specificity of CancerSEEK was > 99%: only 7 of 812 healthy controls scored positive. In addition, CancerSEEK localized the cancer to a small number of anatomic sites in a median of 83% of the patients.

  Study EGAS00001002764

• GCP study

  Study EGAS00001004959

• Mutational spectrum of highly differentiated, fusion-negative rhabdomyosarcoma (set 2).

  Pediatric PAX-FOXO1 fusion-negative rhabdomyosarcoma represents a diverse spectrum of tumors. In this study, the mutational spectrum of 22 fusion-negative rhabdomyosarcomas with high, rhabdomyoma-like levels of differentiation was evaluated using OncoPanel v.2 (OPv2), an Agilent SureSelect custom designed bait set consisting of the coding regions of 504 cancer-relevant genes. Corresponding normal tissue was not available. Discarded normal human skeletal muscle, obtained from 7 donors without tumor history, were also included in the sequencing run.

  Study EGAS00001002771

• Phylogenetic analysis of treatment-naive metastases using whole exome and genome sequencing data

  Metastases are responsible for the majority of cancer related deaths and are often difficult to treat successfully. Even for metastases that occur subsequent to treatment, we do not know whether such relapsing metastases were originally heterogeneous or if the observed heterogeneity is a consequence of therapy. Given that treatment can influence evolutionary dynamics by selecting resistant clones, imposing bottlenecks on cancer cell populations, and even inducing novel somatic mutations, characterizing the prior standing variation among metastases remains an important goal to predict initial therapeutic response. To quantify the heterogeneity at clinical presentation of advanced disease, we surveyed the literature for patients in which at least two treatment-naïve metastases underwent genome/exome-wide sequencing. Across all cancer types surveyed, only 18 subjects were found to fulfill this requirement. Including previously unpublished data from two subjects, we analyzed data of 74 untreated metastases and inferred cancer phylogenies. Putative driver gene mutations were acquired at a 2-fold higher rate on the trunk of all metastases than on branches. Mutations in driver genes along the trunk were strongly enriched for predicted functional consequences. Using a stochastic mathematical model, we find that driver gene heterogeneity among metastases mostly occurs in slowly growing cancers for highly advantageous driver gene mutations. Seeding efficiency only weakly affects the heterogeneity among metastases. These results explain why functional driver gene heterogeneity is uncommon in advanced disease prior to treatment, thus providing optimism for future therapies that depend on mutations across metastases.

  Study EGAS00001002777

• Evolutionary analysis of pancreatic cancer and coexistent precursor lesions using whole exome sequencing data

  Most adult carcinomas develop from noninvasive precursor lesions, a progression that is supported by genetic analysis. Further, the evolution of these lesions contextualizes the dynamics of advanced stage disease. We analyzed the somatic variants of co-existing pancreatic cancers and precursor lesions sampled from distinct regions of the same pancreas. After inferring evolutionary relationships, we found that the ancestral cell had initiated and clonally expanded to form one or more lesions, and that subsequent driver gene mutations eventually led to a pancreatic cancer. We also found that this multi-step progression generally spans many years. Our data suggest that independent, high-grade pancreatic lesions observed in a histologic cross section often represent a single neoplasm that can spread and colonize the ductal system, accumulating spatial and genetic divergence over time.

  Study EGAS00001002778

• Preferential infiltration of distinct Vγ9δ2 T cells into Glioblastoma multiforme

  Glioblastoma multiforme (GBM), the most fatal CNS cancer, is highly infiltrative as a result of phenotypic alteration of cancer cells mainly driven by a mutual interaction among cancer cells, tumor-associated macrophages (TAMs) and other stromal cells. This work aims at characterizing GBM-infiltrating γδ T cells that may regulate the GBM tumor microenvironment and cancer cell gene expression. V(D)J repertoires of tumor-infiltrating and blood circulating γδ T cells from 4 patients were analyzed by NGS-based TCR sequencing. RNA gene expression profiling and immunostaining of cancer tissues were performed as well.

  Study EGAS00001002790

• Deep single-cell RNA sequencing data for 11138 T cells from tumour, adjacent normal tissue and peripheral blood of treatment-naive CRC patients. The DATA ACCESS AGREEMENT is provided at https://github.com/zhangyybio/single-T-cell-data-access. Applicants can request access to the data by directly downloading it or by sending an email to cancerpku@pku.edu.cn. The process that is used to approve an application includes verifying the institution, participants and research purposes of the application. In general this process will take about two weeks. In principal, any scientific research program complying with the laws and bioethic regulation policies of China will be approved.

  T cells are central players in cancer immunotherapy1, yet some of their fundamental properties such as development and migration within tumours remain elusive. The enormous T cell receptor (TCR) repertoire, required for recognising foreign and self-antigens2,3, could serve as lineage tags to track these T cells in tumours4. Here, we obtained transcriptomes of 11,138 single T cells from 12 colorectal cancer (CRC) patients and developed STARTRAC (Single T-cell Analysis by Rna-seq and Tcr TRACking) indices to quantitatively analyse dynamic relationships among 20 identified T cell subsets with distinct functions and clonalities. While both CD8+ effector and “exhausted” T cells exhibited high clonal expansion, they were independently connected with tumour-resident CD8+ effector memory cells, implicating a TCR-based fate decision. Of the CD4+ T cells, the majority of tumour-infiltrating Tregs showed clonal exclusivity, whereas certain Treg clones were developmentally linked to multiple TH clones. Notably, we identified two IFNG+ TH1-like clusters in tumours, the GZMK+ TEM and CXCL13+ TH1-like clusters, which were associated with distinct IFN-γ-regulating transcription factors, EOMES/RUNX3 and BHLHE40, respectively. Only CXCL13+BHLHE40+ TH1-like cells were preferentially enriched in tumours of microsatellite-instable (MSI) patients, which might explain their favourable response rates to immune-checkpoint blockade. Furthermore, we found IGFLR1 to be highly expressed in both CXCL13+BHLHE40+ TH1-like and CD8+ exhausted T cells and possessed co-stimulatory functions. Our integrated STARTRAC analyses provides a powerful avenue to comprehensively dissect the T cell properties in CRC, which could shed new insights into the dynamic relationships of T cells in other cancers

  Study EGAS00001002791

• Age-related remodeling of apparently normal esophageal epithelia by common cancer drivers

  Driver mutated clones multi-focally emerged from early adulthood and over years, increase their number and size, ultimately remodeling the entire esophageal epithelia in extreme elderly. Our results suggest that clonal expansion in esophageal epithelia is an inevitable consequence of normal aging, differentially impacting the development of cancer depending on mutation type and exposure to drinking and smoking.

  Study EGAS00001003008

• Breast cancer DNA repair

  Tumors of germline BRCA1/2 mutated carriers show homologous recombination (HR) deficiency (HRD), resulting in impaired DNA double strand break (DSB) repair and high sensitivity to Poly-(ADP-Ribose)-Polymerase (PARP) inhibitors. Although this therapy is expected to be effective beyond germline BRCA1/2 mutated carriers, a robust validated test to detect HRD tumors is lacking. In the present study we therefore evaluated a functional HR assay exploiting the formation of RAD51 foci in proliferating cells after ex vivo irradiation of fresh breast cancers (BrC) tissue: the RECAP test.Methods Fresh samples of 170 primary BrC were analyzed using the RECAP test. The molecular explanation for the HRD phenotype was investigated by exploring BRCA deficiencies, mutational signatures, tumor infiltrating lymphocytes (TILs) and microsatellite instability (MSI).Results RECAP was completed successfully in 148 out of 170 samples (87%). 24 tumors showed HRD (16%), while 6 tumors were HR intermediate (HRi) (4%). HRD was explained by BRCA deficiencies (mutations, promoter hypermethylation, deletions) in 16 cases. Several non-BRCA deficient HRD tumors showed BRCAness mutational signatures, suggesting that they are also bona fide HRD cases. HRD tumors showed an increased incidence of high TIL counts (p=0.023) compared to HR proficient (HRP) tumors and MSI was more frequently observed in the HRD group (2/20, 10%) than expected in BrC (1%) (p=0.017).Conclusion The RECAP test is a robust assay detecting both BRCA1/2 deficient and BRCA1/2 proficient HRD tumors, suggesting that this test identifies approximately 50% more patients that may benefit from PARPi treatment than BRCA gene testing only.

  Study EGAS00001002792

• Sensitive and Frequent Identification of High Avidity Neo-epitope Specific CD8 + T-cells in Immunotherapy-naïve Ovarian Cancer

  Immunotherapy directed against private tumor neo-antigens derived from non-synonymous somatic mutations is a promising strategy of personalized cancer immunotherapy. However, feasibility in low mutational load tumor types remains unknown. Comprehensive and deep analysis of circulating and tumor-infiltrating lymphocytes (TILs) for neo-epitope specific CD8 + T cells allowed prompt identification of oligoclonal and polyfunctional such cells from most immunotherapy-naïve patients with advanced epithelial ovarian cancer studied. Neo-epitope recognition was discordant between circulating T cells and TILs, and was more likely to be found among TILs, which displayed higher functionalavidity and unique TCRs with higher predicted affinity than their blood counterparts. Our results imply that identification of neo-epitope specific CD8 + T cells is achievable even in tumors with relatively low number of somatic mutations, and neo-epitope validation in TILs extends opportunities for mutanome-based personalized immunotherapies to such tumors.

  Study EGAS00001002803

• Prostate Cancer and Normal Adjacent Prostate RNA-seq samples, NGS-ProToCol

  The dataset "Prostate Cancer and Normal Adjacent Prostate RNA-seq samples, NGS-ProToCol" includes 41 Normal Adjacent Prostate and 51 ribo-depleted Prostate Cancer RNA-seq samples. ---- Detection of fusion transcripts and their genomic breakpoints from RNA sequencing data Youri Hoogstrate, Malgorzata A. Komor, René Böttcher, Job van Riet, Harmen J. G. van de Werken, Stef van Lieshout, Ralf Hoffmann, Evert van den Broek, Anne S. Bolijn, Natasja Dits, Daoud Sie, David van der Meer, Floor Pepers, Chris H. Bangma, Geert J. L. H. van Leenders, Marcel Smid, Pim French, John W.M. Martens, Wilbert van Workum, Peter J. van der Spek, Bart Janssen, Eric Caldenhoven, Christian Rausch, Mark de Jong, Andrew P. Stubbs, Gerrit A. Meijer, Remond J.A. Fijneman, Guido Jenster

  Study EGAS00001002816

• Molecular subtypes of malignant peritoneal mesothelioma

  Malignant Peritoneal Mesothelioma (PeM) is a rare but frequently fatal cancer that originates from the peritoneal lining of the abdomen. Standard treatment of PeM is limited to cytoreductive surgery and/or chemotherapy, and no targeted therapies for PeM yet exist. This study performs comprehensive integrative analysis of genome, transcriptome, and proteome of treatment-naive PeM tumors with the aim of identifying mesothelioma-related molecular alterations and potentially identifying novel treatment strategies.

  Study EGAS00001002820

• Genomic profiling of ovarian adult type granulosa cell tumors

  To investigate the genomic landscape of primary and recurrent ovarian adult type granulosa cell tumors, we first identified an exploratory cohort comprised of cryopreserved surgical biopsies from 24 patients (primary, n = 8; recurrent, n = 16) with 20 having matched normal tissue or peripheral blood samples. We performed whole exome sequencing (WES) on these tumor samples at 200X target coverage (mean 226; range 165-296) and also performed WES on the available normal samples. In addition, we performed cancer gene panel sequencing using the T200.1 hybrid capture platform on FFPE tissue from 55 additional patients (primary, n = 27; recurrent, n = 28), of which we sequenced matched normal tissue for a total of 44.

  Study EGAS00001002833

• The interface of malignant and immunologic clonal dynamics in high-grade serous ovarian cancer

  High-grade serous ovarian cancer exhibits extensive intratumoral heterogeneity coupled with widespread intraperitoneal disease. Despite this, metastatic spread of tumor clones is non-random, implying the existence of local microenvironmental factors that shape tumor progression. We interrogated the molecular interface between tumorinfiltrating lymphocytes (TIL) and cancer cells in 143 samples from 21 patients using whole-genome sequencing, immunohistochemistry, histologic image analysis, gene expression profiling, and T- and B-cell receptor sequencing. We identify 3 immunologic response categories, which frequently co-exist within individual patients. Furthermore, epithelial CD8+ TIL were inversely associated with malignant cell diversity, evidenced by subclonal neoepitope elimination and spatial tracking between tumor and T-cell clones. Intersecting mutational signatures and immune analysis showed that foldback inversion genomic aberrations lead to worse outcomes even in the presence of cytotoxic TIL (n=433). Thus, regional variation in immune contexture mirrors the pattern of intraperitoneal malignant spread, provoking new perspectives for treatment of this challenging disease.

  Study EGAS00001002839

• Clinical data of breast cancer patients from EuCanImage - Use case 7

  This study is part of EuCanImage project. It contains the standardized clinical information following FHIR model. The data was collected together with MRI of patients diagnosed with breast cancer

  Study EGAS50000000191

• A novel breast cancer cell line derived from a metastatic bone lesion of a breast cancer patient

  Purpose: We sought to generate and characterize a novel cell line from a breast cancer bone metastasis in order to better study the progression of the disease.Methods: The cell line, P7731, was derived from a metastatic bone lesion of a breast cancer patient and assessed for marker expression. P7731 was analyzed for DNA copy number variation, somatic mutations and gene expression and compared to the primary tumor. Results: P7731 cells are negative for estrogen receptor alpha (ERα), progesterone receptor (PR) and HER2 (triple-negative), strongly express vimentin (100% of cells positive) and also express cytokeratins 8/18 and 19 but at lower frequencies. Flow cytometry indicates P7731 cells are predominantly CD44+/CD49f+/EpCAM-, consistent with a primitive, mesenchymal-like phenotype. The cell line is tumorigenic in immunocompromised mice. Exome sequencing identified a total of 45 and 76 somatic mutations in the primary tumor and cell line respectively, of which 32 were identified in both samples and included mutations in known driver genes PIK3CA, TP53 and ARID1A. P7731 retains the DNA copy number alterations present in the matching primary tumor. Homozygous deletions detected in the cell line and in the primary tumor were found in regions containing three known (CDKN2A, CDKN2B and CDKN1B) and 23 putative tumor suppressor genes. Cell line specific gene amplification coupled with mRNA expression analysis revealed genes and pathways with potential pro-metastatic functions.Conclusion: This novel human breast cancer-bone metastasis cell line will be a useful model to study aspects of breast cancer biology, particularly metastasis-related changes from breast to bone.

  Study EGAS00001002840