Clinical genome and transcriptome sequencing in younger adults with advanced-stage cancer across all histologies: DKFZ-HIPO Project H021 (http://www.hipo-heidelberg.org/hipo2/index.php/menu-item-2/32-021-prospective-genetic-characterization-of-tumors-from-individual-patients-of-special-interest) / NCT MASTER (http://www.nct-heidelberg.de/forschung/nct-master.html)
This study includes 12 paired samples of Korean AML-ETO paitients.12 AML-ETO tumor samples are paired with each normal(Saliva or BM derived) sequencing data.The results of this WGS study were analyzed by Mutect and GATK for ranking germline variants and cancer variants to make mutational profile matrix.
This study includes 10 paired samples of 2015 Korean AML-ETO paitients.10 AML-ETO tumor samples are paired with each normal(Saliva or BM derived) sequencing data.The results of this WGS study were analyzed by Mutect and GATK for ranking germline variants and cancer variants to make mutational profile matrix.
This study includes 2 paired samples of 2015 Korean AML-ETO paitients. 2 AML-ETO tumor samples are paired with each normal(Saliva or BM derived) sequencing data.The results of this WGS study were analyzed by Mutect and GATK for ranking germline variants and cancer variants to make mutational profile matrix.
Diffuse Intrinsic Pontine Glioma (DIPG) is a fatal brain cancer that arises in the brainstem of children with no effective treatment. To understand what drives DIPGs we integrated whole-genome-sequencing with methylation, expression and copy-number profiling.
Endometriosis, defined as the presence of ectopic endometrial stroma and epithelium, affects approximately 10% of reproductive-age women and can cause pelvic pain and infertility. Endometriotic lesions are considered to be benign inflammatory lesions but have cancerlike features such as local invasion and resistance to apoptosis
March 2018 cumulative data release (bams,fastqs) for reference epigenomes generated at Centre for Epigenome Mapping Technologies, Genome Sciences Center, B.C. Cancer Agency as part of the International Human Epigenome Consortium
The present series corresponds to 24 whole genome sequencing (12 Tumoral/Non-tumoral pairs). Hepatocellular carcinoma (HCC) accounts for more than 90% of liver cancers, and is a major health problem. It is the 3rd cause of cancer-related mortality. Advances in genomic analyses have formed a comprehensive understanding of different underlying pathobiological layers resulting in hepatocarcinogenesis. Thus, the development of next-generation sequencing technologies has made it possible to generate more comprehensive catalogues of somatic alteration events (single nucleotide substitutions, structural variations, and epigenetic changes) in liver cancer genome than ever before.
This dataset pertains to mitochondrial DNA amplicon sequencing of paired DNA samples from gingivo-buccal oral cancer patients. DNA was isolated from the tumor and blood tissues of 89 patients (178 samples). The sequencing libraries were prepared from whole mitochondrial amplicons using Nextera XT DNA Library Preparation Kit (Illumina) and sequenced in Illumina HiSeq platform. The uploaded BAM files are generated by aligning paired-end reads to the mitochondrial reference sequence (rCRS) using BWA-MEM.
In this study, we aim to characterise the landscape of mutation and clonal selection in the human bladder. The data in this study will be generated by whole-genome sequencing of laser-dissected microbiopsies from the bladder. The samples utilised in this study will include urothelium from transplant donors with no history of bladder cancer and cystectomy specimens from patients with bladder cancer. . This dataset contains all the data available for this study on 2020-05-05.
Whole-exome sequencing of 30 early breast cancer samples.
To characterize the subclonal genomic architecture of non-androgen-deprived metastatic prostate cancer, we performed whole-genome sequencing (WGS) of pelvic lymph node metastases and matching noncancerous blood from 10 patients to an average sequencing depth of 55x. The patients are part of PELICAN (Project to ELIminate Lethal Cancer) study led by G. Steven Bova at Johns Hopkins University (USA) and Tampere University (Finland). As of September 2020, study using these data is: Wedge et al, Nature Genetics 2018 (PMID: 29662167)
The dataset is based on 37 FFPE samples obtained from 12 patients diagnosed with breast or larynx cancer, For each patient 3 sample types were obtained P - primary tumor, L - malignant lymph node and C - benign lymph node (control). For patient G46 two malignant lymph nodes were used. DNA isolated from all samples was subject to exome selection using Agilent SureSelect Human All Exon V7. The obtained material was sequenced using NovaSeq 6000 platform with 2x150 reads. The sequencing was conducted by Novogene company.
The Genetics and Epidemiology of Colorectal Cancer Consortium (GECCO) is a collaborative effort comprised of a coordinating center and scientific researchers from well-characterized cohort and case-control studies conducted in North America and Europe. This international consortium aims to accelerate the discovery of common and rare genetic risk variants for colorectal cancer by conducting large-scale meta-analyses of existing and newly generated genome-wide association study (GWAS) data, replicating and fine-mapping of GWAS discoveries, and investigating how genetic risk variants are modified by environmental risk factors. To expand these efforts, we assembled case-control sets or nested case-control sets from 20 different North American or European studies. Summary descriptions and study participant inclusions/exclusion criteria for each of these studies are detailed below. The Black Women's Health Study (BWHS): Is the largest follow-up study of the health of African-American women (Cozier et al., 2004; Rosenberg et al., 1995) [PMID: 15018884; PMID: 7722208]. The purpose is to identify and evaluate causes and preventives of cancers and other serious illnesses in African-American women. Among the diseases being studied are breast cancer, colorectal cancer, type 2 diabetes, uterine fibroids, systemic lupus erythematosus, and cardiovascular disease. The study began in 1995, when 59,000 black women from all parts of the United States enrolled through postal questionnaires. The women provided demographic and health data on the 1995 baseline questionnaire, including information on weight, height, smoking, drinking, contraceptive use, use of other selected medications, illnesses, reproductive history, physical activity, diet, use of health care, and other factors. The participants are followed through biennial questionnaires to determine the occurrence of cancers and other illnesses and to update information on risk factors. Self-reports of cancer are confirmed through medical records and state cancer registry records. Mouthwash-swish samples, as a source of DNA, were obtained from ~26,000 BWHS participants in 2002-2007. DNA was isolated from the mouthwash-swish samples at the Boston University Molecular Core Genetics Laboratory using the QIAAMP DNA Mini Kit (Qiagen). All incident colorectal cancer cases with a DNA sample were included in the present analysis. Two controls per case, selected from among BWHS participants free of colorectal cancer at end of follow-up, were matched to cases on year of birth (+/- 2 years) and geographical region of residence (Northeast, South, Midwest, and West). A total 209 colorectal cancer cases and 423 controls were sent for genotyping. Campaign Against Cancer and Heart Disease (CLUE II): The Campaign Against Cancer and Heart Disease, is a prospective cohort designed to identify biomarkers and other factors associated with risk of cancer, heart disease, and other conditions (Kakourou et al., 2015) [PMID: 26220152]. 32,894 participants were recruited from May through October 1989 from Washington County, Maryland and surrounding communities. Colorectal cancer cases (n = 297) and matched controls (n = 296) were identified between 1989 and 2000 among participants in the CLUE II cohort of Washington County, Maryland. Colorectal Cancer Study of Austria (CORSA): In the ongoing colorectal cancer study of Austria (CORSA), more than 13,000 Caucasian participants have been recruited within the province-wide screening project "Burgenland Prevention Trial of Colorectal Disease with Immunological Testing" (B-PREDICT) since 2003 (Hofer et al., 2011) [PMID: 21422235]. All inhabitants of the Austrian province Burgenland aged between 40 and 80 years are annually invited to participate in fecal immunochemical testing and haemoccult positive screening participants are invited for colonoscopy. CORSA includes genomic DNA and plasma of colorectal cancer cases, low-risk and high-risk adenomas, and colonoscopy-negative controls. Controls received a complete colonoscopy and were free of colorectal cancer or polyps. CORSA participants have been recruited in the four KRAGES hospitals in Burgenland, Austria, and additionally, at the Medical University of Vienna (Department of Surgery), the Viennese hospitals "Rudolfstiftung" and the "Sozialmedizinisches Zentrum Sud", and at the Medical University of Graz (Department of Internal Medicine). 1403 colorectal cancer and advanced colorectal adenoma cases, and 1404 matched controls were selected for the study. Distribution of factors sex and age (5 year strata) were evenly matched between cases and controls. Cancer Prevention Study II (CPS II): The CPS II Nutrition cohort is a prospective study of cancer incidence and mortality in the United States, established in 1992 and described in detail elsewhere (Calle et al., 2002; Campbell et al., 2014) [PMID: 12015775; PMID: 25472679]. At enrollment, participants completed a mailed self-administered questionnaire including information on demographic, medical, diet, and lifestyle factors. Follow-up questionnaires to update exposure information and to ascertain newly diagnosed cancers were sent biennially starting in 1997. Reported cancers were verified through medical records, state cancer registry linkage, or death certificates. The Emory University Institutional Review Board approves all aspects of the CPS II Nutrition Cohort. A total of 360 cases and 359 controls were selected for this study. Czech Republic Colorectal Cancer Study (Czech Republic CCS): Cases with positive colonoscopy results for malignancy, confirmed by histology as colon or rectal carcinomas, were recruited between September 2003 and May 2012 in several oncological departments in the Czech Republic (Prague, Pilsen, Benesov, Brno, Liberec, Ples, Pribram, Usti and Labem, and Zlin). Two control groups, sampled at the same time of cases recruitment, were included in the study. The first group consisted of hospital-based individuals with a negative colonoscopy result for malignancy or idiopathic bowel diseases. The reasons for the colonoscopy were: i) positive fecal occult blood test, ii) hemorrhoids, iii) abdominal pain of unknown origin, and iv) macroscopic bleeding. The second control group consisted of healthy blood donor volunteers from a blood donor center in Prague. All individuals were subjected to standard examinations to verify the health status for blood donation and were cancer-free at the time of the sampling. Details of CRC cases and controls have been reported previously (Vymetalkova et al., 2014; Naccarati et al., 2016; Vymetalkova et al., 2016) [PMID: 24755277; PMID: 26735576; PMID: 27803053]. All subjects were informed and provided written consent to participate in the study. They approved the use of their biological samples for genetic analyses, according to the Declaration of Helsinki. The design of the study was approved by the Ethics Committee of the Institute of Experimental Medicine, Prague, Czech Republic. All subjects included in the study were Caucasians and comprised 1792 cases and 1764 matched controls. Controls were matched to CRC cases as 1:1 ratio. Matching was done on age and sex. Age was matched on +-5 years, whereas sex was matched exactly. For the cases without matched controls, matching was done only on sex. Early Detection Research Network (EDRN): The aim of the EDRN initiative is to develop and sustain a biorepository for support of translational research (Amin et al., 2010) [PMID: 21031013]. High-quality biospecimens were accrued and annotated with pertinent clinical, epidemiologic, molecular and genomic information. A user-friendly annotation tool and query tool was developed for this purpose. The various components of this annotation tool include: CDEs are developed from the College of American Pathologists (CAP) Cancer Checklists and North American Association of Central Cancer Registries (NAACR) standards. The CDEs provides semantic and syntactic interoperability of the data sets by describing them in the form of metadata or data descriptor. A total of 352 colorectal case samples and 399 controls were selected for this study. Controls were matched to CRC cases based on age and sex. The EPICOLON Consortium (EPICOLON): The EPICOLON Consortium comprises a prospective, multicentre and population-based epidemiology survey of the incidence and features of CRC in the Spanish population (Fernandez-Rozadilla et al., 2013) [PMID: 23350875]. Cases were selected as patients with de novo histologically confirmed diagnosis of colorectal adenocarcinoma. Patients with familial adenomatous polyposis, Lynch syndrome or inflammatory bowel disease-related CRC, and cases where patients or family refused to participate in the study were excluded. Hospital-based controls were recruited through the blood collection unit of each hospital, together with cases. All of the controls were confirmed to have no history of cancer or other neoplasm and no reported family history of CRC. Controls were randomly selected and matched with cases for hospital, sex and age (+- 5 years). A total of 370 cases and 370 controls were selected for genotyping. Hawaii Adenoma Study: For this adenoma study, two flexible-sigmoidoscopy screening clinics were first used to recruit participants on Oahu, Hawaii. Adenoma cases were identified either from the baseline examination at the Hawaii site of the Prostate Lung Colorectal and Ovarian cancer screening trial during 1996-2000 or at the Kaiser Permanente Hawaii's Gastroenterology Screening Clinic during 1995-2007. In addition, starting in 2002 and up to 2007, we also approached for recruitment all eligible patients who underwent a colonoscopy in the Kaiser Permanente Hawaii Gastroenterology Department. Cases were patients with histologically confirmed first-time adenoma(s) of the colorectum and were of Japanese, Caucasian or Hawaiian race/ethnicity. Controls were selected among patients with a normal colorectum and were individually matched to the cases on age at exam, sex, race/ethnicity, screening date (+-3 months) and clinic and type of examination (colonoscopy or flexible sigmoidoscopy). We recruited 1016 adenoma cases (67.8% of all eligible) and 1355 controls (69.2% of all eligible); 889 cases and 1169 controls agreed to give a blood and 29 cases and 34 controls, a mouthwash sample. A total of 989 cases and 1185 controls were genotyped for this study. Columbus-area HNPCC Study (HNPCC, OSUMC): Patients with colorectal adenocarcinoma diagnosed at six participating hospitals were eligible for this study, regardless of age at diagnosis or family history of cancer. Patients with a clinical diagnosis of familial adenomatous polyposis were not eligible for this study. These six hospitals perform the vast majority of all operations for CRC in the Columbus metropolitan area (population 1.7 million). The institutional review board at all participating hospitals approved the research protocol and consent form in accordance with assurances filed with and approved by the United States Department of Health and Human Services. Briefly, during the period of January 1999 through August 2004, 1,566 eligible patients with CRC were accrued to the study (Hampel et al., 2008) [PMID 18809606]. A total of 1472 colorectal cancer samples had enough blood DNA remaining to be sent for genotyping. Control samples were provided by the Ohio State University Medical Center%#39;s (OSUMC) Human Genetics Sample Bank. The Columbus Area Controls Sample Bank is a collection of control samples for use in human genetics research that includes both donors' anonymized biological specimens and linked phenotypic data. The data and samples are collected under the protocol "Collection and Storage of Controls for Genetics Research Studies", which is approved by the Biomedical Sciences Institutional Review Board at OSUMC. Recruitment takes place in OSUMC primary care and internal medicine clinics. If individuals agree to participate, they provide written informed consent, complete a questionnaire that includes demographic, medical and family history information, and donate a blood sample. 4-7 ml of blood is drawn into each of 3 ACD Solution A tubes and is used for genomic DNA extraction and the establishment of an EBV-transformed lymphoblastoid cell culture, cell pellet in Trizol, and plasma. Controls were matched to CRC cases as 1:1. Matching was done on age at reference time (age_ref), race, and sex. Age_ref was matched on +-5 years. Sex and race were matched exactly. For the cases without matched controls, matching was done only on sex and race with 1:1 ratio. Since controls are fewer than cases, one control is matched on 2 cases at most. Health Professionals Follow-up Study (HPFS): A parallel prospective study to the NHS (Nurses' Health Study). The HPFS cohort comprised 51,529 men aged 40-75 who, in 1986, responded to a mailed questionnaire (Rimm et al., 1990) [PMID: 2090285]. Participants provided information on health related exposures, including current and past smoking history, age, weight, height, diet, physical activity, aspirin use, and family history of colorectal cancer. Colorectal cancer and other outcomes were reported by participants or next-of-kin and were followed up through review of the medical and pathology record by physicians. Overall, more than 97% of self-reported colorectal cancers were confirmed by medical record review. Information was abstracted on histology and primary location. Incident cases were defined as those occurring after the subject provided the blood sample. Prevalent cases were defined as those occurring after enrollment in the study but before the subject provided the blood sample. Follow-up evaluation has been excellent, with 94% of the men responding to date. Colorectal cancer cases were ascertained through January 1, 2008. In 1993-1995, 18,825 men in the HPFS mailed blood samples by overnight courier, which were aliquoted into buffy coat and stored in liquid nitrogen. In 2001-2004, 13,956 men in the HPFS who had not provided a blood sample previously mailed in a swish-and-spit sample of buccal cells. Incident cases were defined as those occurring after the subject provided a blood or buccal sample. Prevalent cases were defined as those occurring after enrollment in the study in 1986, but before the subject provided either a blood or buccal sample. After excluding participants with histories of cancer (except nonmelanoma skin cancer), ulcerative colitis, or familial polyposis, case-control sets were previously constructed. In addition to colorectal cancer cases and controls, a set of adenoma cases and matched controls with available DNA from buffy coat were selected for genotyping. Over the follow-up period, data were collected on endoscopic screening practices and, if individuals had been diagnosed with a polyp, the polyps were confirmed to be adenomatous by medical record review. Adenoma cases were ascertained through January 1, 2008. A separate case-control set was constructed of participants diagnosed with advanced adenoma matched to control participants who underwent a lower endoscopy in the same time period and did not have an adenoma. Advanced adenoma was defined as an adenoma 1 cm or larger in diameter and/or with tubulovillous, villous, or highgrade dysplasia/carcinoma-in-situ histology. Matching criteria included year of birth (within 1 year) and month/ year of blood sampling (within 6 months), the reason for their lower endoscopy (screening, family history, or symptoms), and the time period of any prior endoscopy (within 2 years). Controls matched to cases with a distal adenoma either had a negative sigmoidoscopy or colonoscopy examination, and controls matched to cases with proximal adenoma all had a negative colonoscopy. In total, 159 advanced adenoma cases and 109 controls were selected for genotyping. Leeds Colorectal Cancer Study (LCCS): Following local ethical approval, colorectal cancer cases were recruited from 1997 until 2012 in Leeds, UK through surgical clinics. Initially, funding was provided by the UK Ministry of Agriculture, Farming and Fisheries (subsequently the Food Standards Agency) and Imperial Cancer Research Fund (subsequently Cancer Research UK). Recruitment also occurred similarly in Dundee, Perth and York between the periods of 1997 and 2001 using the same protocol and the data and samples were combined. Pathologically confirmed cases were consented at outpatient clinics, providing information on known and postulated risk factors for colorectal cancer (diet, lifestyle and family history) as well as providing a blood sample for DNA. Exclusion criteria included pre-existing diverticular disease and an inability to complete the questionnaire. The General Practitioners of cases (all UK residents have a nominated General Practitioner to whom to refer initial medical queries) and these GPs were asked to send letters to other persons on their patient list of the same gender and born within 5 years of the case. Subsequently to enhance the number of controls, we systematically invited patients from selected GP practices. Diet was assessed in cases and controls using an extensive dietary and lifestyle questionnaire modified by that produced by the European Prospective Investigation in Cancer (EPIC). The frequency that each specific food items were eaten was recorded and we also obtained average fruit and vegetable consumption as a cross-check. In total, 1591 cases and 739 controls provided a DNA sample. The North Carolina Colon Cancer Studies (NCCCS I/II): The North Carolina Colon Cancer Studies (NCCCS I- colon and NCCCS II-rectal) were population-based case-control studies conducted in 33 counties of North Carolina. Cases were identified using the rapid case ascertainment system of the North Carolina Central Cancer Registry. Patients with a first diagnosis of histologically confirmed invasive adenocarcinoma of the colon (cecum through sigmoid colon) between October 1996 and September 2000 were classified as potential cases in the NCCCS I. The NCCCS II included patients with a first diagnosis of histologically confirmed invasive adenocarcinoma of the sigmoid colon, rectosigmoid, or rectum (hereafter collectively referred to as rectal cancer) between May 2001 and September 2006. Additional eligibility requirements were: aged 40-80 years, residence in one of the 33 counties, ability to give informed consent and complete an interview, had a driver's license or identification card issued by the North Carolina Department of Motor Vehicles (if under the age of 65), and had no objections from the primary physician in regards to contacting the individual. Controls, identified and sampled during the respective study dates, were selected from two sources. Potential controls under the age of 65 were identified using the North Carolina Department of Motor Vehicles records. For those 65 years and older, records from the Center for Medicare and Medicaid Services were used. Controls were matched to cases using randomized recruitment strategies. Recruitment probabilities were done using strata of 5-year age, sex, and race groups. Dietary information was collected using a modified version of the semiquantitative food frequency questionnaire developed at the National Cancer Institute. In addition, participants were asked about vitamin and mineral supplementation, special diets, restaurant eating, sodium use, and fats used in cooking. In NCCCS I, 515 colorectal cases and 687 matched controls were sent for genotyping. In NCCCS II, 796 colorectal cases and 823 controls were sent from the NCCCS II for genotyping. Controls were matched to CRC cases as 1:1 ratio. Matching was done on age, race, and sex. Age was matched on +-5 years. Race and sex was matched exactly. For the cases without matched controls, matching was done only on sex and race. Nurses Health Study (NHS): The NHS cohort began in 1976 when 121,700 married female registered nurses age 30-55 years returned the initial questionnaire that ascertained a variety of important health-related exposures (Belanger et al., 1978) [PMID: 248266]. Since 1976, follow-up questionnaires have been mailed every 2 years. Colorectal cancer and other outcomes were reported by participants or next-of-kin and followed up through review of the medical and pathology record by physicians. Overall, more than 97% of self-reported colorectal cancers were confirmed by medical-record review. Information was abstracted on histology and primary location. The rate of follow-up evaluation has been high: as a proportion of the total possible follow-up time, follow-up evaluation has been more than 92%. Colorectal cancer cases were ascertained through June 1, 2008. In 1989 -1990, 32,826 women in NHS I mailed blood samples by overnight courier, which were aliquoted into buffy coat and stored in liquid nitrogen. In 2001-2004, 29,684 women in NHS I who did not previously provide a blood sample mailed a swish-and-spit sample of buccal cells. Incident cases were defined as those occurring after the subject provided a blood or buccal sample. Prevalent cases were defined as those occurring after enrollment in the study in 1976 but before the subject provided either a blood or buccal sample. After excluding participants with histories of cancer (except nonmelanoma skin cancer), ulcerative colitis, or familial polyposis, case-control sets were previously constructed from which DNA was isolated from either buffy coat or buccal cells for genotyping. In addition to colorectal cancer cases and controls, a set of advanced adenoma cases and matched controls with available DNA from buffy coat were selected for genotyping. Over the follow-up period, data were collected on endoscopic screening practices and, if individuals had been diagnosed with a polyp, the polyps were confirmed to be adenomatous by medical record review. Adenoma cases were ascertained through June 1, 2011. A separate case-control set was constructed of participants diagnosed with advanced adenoma matched to control participants who underwent a lower endoscopy in the same time period and did not have an adenoma. Advanced adenoma was defined as an adenoma more than 1 cm in diameter and/or with tubulovillous, villous, or high-grade dysplasia/carcinoma-in-situ histology. Matching criteria included year of birth (within 1 year) and month/year of blood sampling (within 6 months), the reason for their lower endoscopy (screening, family history, or symptoms), and the time period of any prior endoscopy (within 2 years). Controls matched to cases with a distal adenoma either had a negative sigmoidoscopy or colonoscopy examination, and controls matched to cases with proximal adenoma all had a negative colonoscopy. A total of 272 cases and 236 matched controls were sent to CIDR for the advanced adenoma case-control set. Northern Swedish Health and Disease Study (NSHDS): Comprises over 110,000 participants, including approximately one third with repeated sampling occasions, from three population-based cohorts (Dahlin et al., 2010; Myte et al., 2016) [PMID: 20197478; PMID: 27367522]. The largest is the ongoing Vasterbotten Intervention Programme, in which all residents of Vasterbotten County are invited to a health examination upon turning 30 (some years), 40, 50 and 60 years of age. Extensive measured and self-reported health and lifestyle data, as well as blood samples for central biobanking in Umea, Sweden, are collected at the health exam. Leucocyte DNA samples for 1:1-matched CRC case-control sets from the NSHDS, of which 878 samples are included in this study, have been selected for genotyping. This is in addition to 354 samples from the NSHDS previously analyzed as part of the multicenter EPIC cohort. Cancer-specific and overall survival data are available for all patients. For at least 425 patients, archival tumor tissue has been analyzed for the BRAF V600E mutation and by sequencing codon 12 and 13 for KRAS mutations, as well as for MSI screening status by immunohistochemistry and for an eight-gene CIMP panel using quantitative real-time PCR (MethyLight). Ohio Colorectal Cancer Prevention Initiative (OCCPI, OSUMC): OCCPI (ClinicalTrials.gov identifier: NCT01850654) is a population-based study of colorectal cancer patients diagnosed in one of 51 hospitals throughout the state of Ohio from January 1, 2013 through December 31, 2016. The OCCPI was created to decrease CRC incidence in Ohio by identifying patients with hereditary predisposition (statewide universal tumor screening for newly diagnosed CRC patients), increase colonoscopy compliance for first-degree relatives of CRC patients, and encourage future research through the creation of a biorepository. The 51 Ohio hospitals participating in the OCCPI were selected to represent a cross-section of clinical centers in the state based on high reported volume of CRC patients, affiliation with a high volume hospital, or interest in participation. Institutional Review Board (IRB) approval was obtained by the individual hospitals, Community Oncology Programs, or by ceding review to the OSU IRB. Written informed consent was obtained. A total of 2139 colorectal cases were genotyped. Patients were considered eligible for this study if they were age 18 or older at the time of enrollment, if they had a surgical resection (or biopsy if unresectable) in the state of Ohio demonstrating an adenocarcinoma of the colorectum from 1/1/13 - 12/31/16. Matched control samples were selected from the Ohio State University Medical Center's (OSUMC) Human Genetics Sample Bank in an identical way to the selection for the Columbus-area HNPCC Study (please refer to the description for the Columbus-area HNPCC Study). Prostate, Lung, Colorectal and Ovarian Cancer Screening Trail (PLCO): PLCO enrolled 154,934 participants (men and women, aged between 55 and 74 years) at ten centers into a large, randomized, two-arm trial to determine the effectiveness of screening to reduce cancer mortality. Sequential blood samples were collected from participants assigned to the screening arm. Participation was 93% at the baseline blood draw. In the observational (control) arm, buccal cells were collected via mail using the "swish-and-spit" protocol and participation rate was 65%. Details of this study have been previously described (Huang et al., 2016) [PMID: 27673363] and are available online (http://dcp.cancer.gov/plco). For this study 1651 advanced adenoma cases and 1392 controls were selected for genotyping. Selenium and Vitamin E Prevention Trial (SELECT): The Selenium and Vitamin E Cancer Prevention Trial (SELECT) was a double-blind, placebo controlled clinical trial which explored using selenium and vitamin E alone and in combination to prevent prostate cancer in healthy men (Lippman et al., 2009) [PMID: 19066370]. Secondary endpoints included the prevention of colorectal and lung cancers. SELECT was conducted at 427 sites and centers in the United States, Canada and Puerto Rico; 35,533 men 55 years and older (50 or older if African American) were randomized beginning August 22, 2001. Supplementation was discontinued on October 23, 2008 due to futility. 308 colorectal cancer cases and 308 matched controls were selected from the SELECT population and sent for genotyping. Screening Markers For Colorectal Disease Study and Colonoscopy and Health Study (SMS-REACH): Details on this study population were previously reported (Burnett-Hartman et al., 2014) [PMID: 24875374]. Participants were enrollees in an integrated health-care delivery system in western Washington State (Group Health Cooperative, Seattle, Washington) aged 24-79 years who underwent an index colonoscopy for any indication between 1998 and 2007 and donated a buccal-cell or blood sample for genotyping analysis. Study recruitment took place in 2 phases, with phase 1 occurring in 1998-2003 and phase 2 occurring in 2004-2007. Persons who had undergone a colonoscopy less than 1 year prior to the index colonoscopy, persons with inadequate bowel preparation for the index colonoscopy, and persons with a prior or new diagnosis of colorectal cancer, a familial colorectal cancer syndrome (such as familial adenomatous polyposis), or another colorectal disease were ineligible. Patients diagnosed with adenomas or serrated polyps and persons who were polyp-free at the index colonoscopy (controls) were systematically recruited during both phases of recruitment. Approximately 75% agreed to participate and provided written informed consent. Based on medical records, persons who agreed to participate and those who refused study participation were similar with respect to age, sex, and colorectal polyp status. Study protocols were approved by the institutional review boards of the Group Health Cooperative and the Fred Hutchinson Cancer Research Center (Seattle, Washington). A total of 575 cases and 508 matched were selected for the study. Controls were matched to CRC cases as 1:1 ratio. Matching was done on age_ref, race, and sex. Age_ref was matched on +-5 years. The Women's Health Initiative (WHI): WHI is a long-term national health study that has focused on strategies for preventing heart disease, breast and colorectal cancer, and osteoporotic fractures in postmenopausal women. The original WHI study included 161,808 postmenopausal women enrolled between 1993 and 1998. The Fred Hutchinson Cancer Research Center in Seattle, WA serves as the WHI Clinical Coordinating Center for data collection, management, and analysis of the WHI. The WHI has two major parts: a partial factorial randomized Clinical Trial (CT) and an Observational Study (OS); both were conducted at 40 Clinical Centers nationwide. The CT enrolled 68,132 postmenopausal women between the ages of 50-79 into trials testing three prevention strategies. If eligible, women could choose to enroll in one, two, or all three of the trial components. The components are: Hormone Therapy Trials (HT): This double-blind component examined the effects of combined hormones or estrogen alone on the prevention of coronary heart disease and osteoporotic fractures, and associated risk for breast cancer. Women participating in this component with an intact uterus were randomized to estrogen plus progestin (conjugated equine estrogens [CEE], 0.625 mg/d plus medroxyprogesterone acetate [MPA] 2.5 mg/d] or a matching placebo. Women with prior hysterectomy were randomized to CEE or placebo. Both trials were stopped early, in July 2002 and March 2004, respectively, based on adverse effects. All HT participants continued to be followed without intervention until close-out. Dietary Modification Trial (DM): The Dietary Modification component evaluated the effect of a low-fat and high fruit, vegetable and grain diet on the prevention of breast and colorectal cancers and coronary heart disease. Study participants were randomized to either their usual eating pattern or a low-fat dietary pattern. Calcium/Vitamin D Trial (CaD): This double-blind component began 1 to 2 years after a woman joined one or both of the other clinical trial components. It evaluated the effect of calcium and vitamin D supplementation on the prevention of osteoporotic fractures and colorectal cancer. Women in this component were randomized to calcium (1000 mg/d) and vitamin D (400 IU/d) supplements or a matching placebo. The Observational Study (OS)examines the relationship between lifestyle, environmental, medical and molecular risk factors and specific measures of health or disease outcomes. This component involves tracking the medical history and health habits of 93,676 women not participating in the CT. Recruitment for the observational study was completed in 1998 and participants were followed annually for 8 to 12 years. All centrally confirmed cases of invasive colorectal cancers, or deaths from colorectal cancer were selected as potential cases from September 30, 2015 database. Controls were participants free of colorectal cancer (invasive or in situ) as of September 30, 2015. Potential cases and controls were excluded if they (1) were non-White; (2) had history of colorectal cancers at baseline; (3) lost to follow-up after enrollment; (4) DbGAP ineligible; (5) had <1.25ug of DNA; (6) selected for WHI study M26 Phase I or II; (7) selected for WHI study AS224 and also included in the imputation project. A total of 578 cases and 104,429 controls met the eligibility criteria. Each case was matched with 1 control (1:1) that exactly met the following matching criteria: age (+-5 years), 40 randomization centers (exact), WHI date (+-3 years), CaD date (+-3 years), OS flag (exact), HRT assignments (exact), DM assignments (exact), and CaD assignments (exact). Control selection was done in a time-forward manner, selecting one control for each case from the risk set at the time of the case's event. The matching algorithm was allowed to select the closest match based on a criteria to minimize an overall distance measure (Bergstralh EJ, Kosanke JL. Computerized matching of cases to controls. Technical Report #56, Department of Health Sciences Research, Mayo Clinic, Rochester MN. April 1995). Each matching factor was given the same weight. When exact matches could not be found, the matching criteria were gradually relaxed among unmatched cases and controls until all cases had found matched controls. Using the matching criteria specified above, 559 of the 578 eligible cases found exact matches. The matching criteria was then relaxed to : Age+-5, randomization centers, WHI date +- 3 years, CaD date +- 3 years, OS flag, HRT flag, DM flag, CaD flag. 17 of the remaining 19 unmatched cases found matched controls. By matching on Age+-5, randomization centers, WHI date +- 3 years, CaD date +- 3 years, OS flag, HRT flag, the remaining 2 unmatched cases found their matches.
Study of the genetic and epigenetic clonal evolution of blood cancers.
Raw methylation data from triple negative breast cancer.
Cervical cancer is responsible for 10-15% of cancer related deaths in women worldwide. The etiological role of infection with high-risk human papilloma viruses (HPV) in carcinomas of the cervix is well established. In general, the development of cervical carcinomas follows a progression from persistent HPV infection through precancerous lesions to invasive cancer. Previous studies have implicated somatic mutations in PIK3CA, PTEN, TP53, STK11 and KRAS as well as chromosome-arm level copy number alterations in the pathogenesis of cervical carcinomas. Here, we report whole exome sequencing analysis of 118 cervical carcinoma-normal paired samples from patients in Norway and Mexico, as well as transcriptome sequencing of 80 cases and whole genome sequencing of 13 tumor-normal pairs. Novel somatic mutations include recurrent E322K substitutions in the MAPK1 gene encoding the ERK2 kinase and inactivating mutations in the HLA-B gene. In addition, recurrent somatic mutations in FBXW7, EP300, and NFE2L2 are novel in the context of primary cervical carcinomas. Analysis of HPV integration sites revealed recurrent integration into the RAD51B locus as well as co-occurrence of HPV genome integration and copy number gains within several genomic loci. These findings shed new light on the pathogenesis of cervical carcinomas and suggest potential novel therapeutic targets.
The goal of this study was to identify SNPs and CNPs that are associated with development of normal tissue toxicities resulting from radiotherapy for prostate cancer. The study population includes approximately 1,400 men treated with brachytherapy, external beam radiation therapy, or a combination of the two treatments, and assessed for adverse effects at baseline and following radiotherapy. Three toxicity endpoints were investigated using a two-stage GWAS approach: urinary morbidity, rectal bleeding and erectile dysfunction. The study sample was split into a discovery set (N=367) and a replication set (N=417), and an additional 647 samples, which were not part of this original cohort, were also included as an independent replication set. The replication set was developed via collaboration developed under the framework of the Radiogenomics Consortium (RGC). The long-term goal of this project, and other radiogenomics projects lead by the RGC, is two-fold: 1) Develop an assay capable of predicting which cancer patients are most likely to develop radiation injuries resulting from treatment with a standard RT protocol, and 2) Obtain information to assist with the elucidation of the molecular pathways responsible for radiation-induced normal tissue toxicities. These studies focus on multiple cancer types including prostate, breast, lung, and head and neck cancers.
The evolutionary steps from primary tumor to metastasis in prostate cancer are largely uncharted, and the ability to use serum, plasma, and cerebrospinal fluid as a correlate of aggregate metastatic tumor genomic status has not been tested. We used deep targeted sequencing to reconstruct tumor evolution in ten prostate cancer patients with fatal disease encompassing examination of the prostate and adjacent and distant organs, as well as plasma, serum, and cerebrospinal fluid at various time points. We show that there is substantial evolution from a common ancestor within the prostate that results in branching to multiple lineages which form an intermixed multi-clonal primary tumor mass. After the occurrence of key driver aberrations, one of these lineages will metastasize to multiple sites in a sequential fashion. These metastatic sites are then susceptible to being populated by cells from other intra-prostatic lineages or from other metastases. Genomic representation of metastases in body fluids is not uniform. Cerebrospinal fluid analysis can detect lineages not detected in circulating DNA, suggesting possible clinical utility.
Signet-ring cell carcinoma (SRCC) has specific epidemiology and oncogenesis in gastric cancer, however with no systematical investigation for prognostic genomic features. We systematically investigated the clinical characteristics of 1,868 Chinese gastric cancer patients, and found that signet-ring cell content was significantly related to multiple clinical characteristics and treatment outcomes. Next, we performed whole genome sequencing for 32 SRCC patients with > 80% signet-ring cells in tumor, and identified frequent5 CLDN18-ARHGAP26/6 fusion (25%). With additional 797 patients for validation, we notice that prevalence of CLDN18-ARHGAP26/6 fusion is positively associated with signet-ring cell content (P = 4.1 x 10 -9 ), younger age at diagnosis (P = 4.2 x 10 -10 ), female/male ratio (P = 1.7 x 10 -9 ), and advanced TNM stage (P = 1.7 x 10 -5 ). Importantly, patients with CLDN18-ARHGAP26/6 fusion had a worse survival outcomes (P = 0.03), and got no benefit0 from platinum/fluoropyrimidines based chemotherapy (P = 0.92) compared to fusion-free patients (P = 0.001), which is consistent with the fact of oxaliplatin/fluoropyrimidine resistance acquired in CLDN18-ARHGAP26 introduced gastric cancer cell lines. Overall, this study provides new insights into the clinical and genomic features of SRCC, and highlights the importance of frequent CLDN18-ARHGAP26/6 fusions in chemotherapy response for SRCC.
The French ICGC project on liver tumors is coordinated by Pr Jessica Zucman-Rossi and funded by Inca (French Institute for Cancer). The aim of the present project is to identify the catalog of somatic and germline mutations in liver tumors using whole genome and whole exome sequencing together with CGH-SNP, methylome and transcriptomic profiling. For this purpose, a series of 500 liver tumors are collected through the French National Liver Collection and these samples will be analyzed using the different omics technologies. The data will be deposited in the ICGC and EGA database to be publically available for the scientific community. Hepatocellular carcinoma (HCC) accounts for more than 90% of liver cancers, and is a major health problem. It is the 3rd cause of cancer-related mortality. Advances in genomic analyses have formed a comprehensive understanding of different underlying pathobiological layers resulting in hepatocarcinogenesis. Thus, the development of next-generation sequencing technologies has made it possible to generate more comprehensive catalogues of somatic alteration events (single nucleotide substitutions, structural variations, and epigenetic changes) in liver cancer genome than ever before. The dataset will include 50 whole genome sequencing tumor/germline pairs, of which 6 are deposited in February 2014.
Immune checkpoint inhibitors (ICI), which target immune regulatory pathways to unleash antitumor responses, have revolutionized cancer immunotherapy. Despite the remarkable success of ICI immunotherapy, a significant proportion of patients whose tumors respond to these treatments develop immune-related adverse events (irAEs) resembling autoimmune diseases. Although the clinical spectrum of irAEs is well characterized, their successful management remains empiric. This is in part because the pathogenic mechanisms involved in the break-down of peripheral tolerance and induction of irAEs remain elusive. Herein, we focused on regulatory T cells (Tregs) in individuals with irAEs because these cells are vital for maintenance of peripheral tolerance, appear expanded in the peripheral blood of individuals with cancer and abundantly express checkpoint molecules, hence representing direct targets of ICI immunotherapy. Our data demonstrate an intense transcriptomic reprogramming of CD4+CD25+CD127– Tregs in the blood of individuals with advanced metastatic melanoma who develop irAEs following ICI immunotherapy, with a characteristic inflammatory, apoptotic and metabolic signature. This inflammatory signature was shared by Tregs from individuals with different types of cancer developing irAEs and individuals with autoimmune diseases. Our findings propose an inflammatory Treg reprogramming as a feature of immunotherapy-induced irAEs, that may facilitate translational approaches aiming to induce robust antitumor immunity without disturbing peripheral tolerance.
Germline mutations in BRCA1 or BRCA2 exist in ~2-7% of breast cancer patients, which has led to the approval of PARP inhibitors in the advanced setting. We have previously reported a phase II neoadjuvant trial of single agent talazoparib for patients with germline BRCA pathogenic variants with a pathologic complete response (pCR) rate of 53%. As nearly half of the patients treated did not have pCR, better strategies are needed to overcome treatment resistance. To this end, we conducted multi-omic analysis of 13 treatment naïve breast cancer tumors from patients that went on to receive single-agent neoadjuvant talazoparib. We looked for biomarkers that were predictive of response (assessed by residual cancer burden) after 6 months of therapy. We found that all resistant tumors exhibited either the loss of SHLD2, expression of a hypoxia signature, or expression of a stem cell signature. These results indicate that the deep analysis of pre-treatment tumors can identify biomarkers that are predictive of response to talazoparib and potentially other PARP inhibitors, and provides a framework that will allow for better selection of patients for treatment, as well as a roadmap for the development of novel combination therapies to prevent emergence of resistance.
Cancer heterogeneity at the proteome level may explain differences in therapy response and prognosis beyond the currently established genomic and transcriptomic based diagnostics. The relevance of proteomics for disease classifications remains to be established in clinically heterogeneous cancer entities such as chronic lymphocytic leukemia (CLL). Here, we characterized the proteome and transcriptome in-depth alongside genetic and ex-vivo drug response profiling in a clinically well annotated CLL discovery cohort (n= 68). Unsupervised clustering of the proteome data revealed six subgroups. Five of these proteomic groups were associated with genetic features, while one group was only detectable at the proteome level. This new group was characterized by accelerated disease progression, high spliceosomal protein abundances associated with aberrant splicing, and low B cell receptor signaling protein abundances (ASB-CLL). We developed classifiers to identify ASB-CLL based on its characteristic proteome or splicing signature in two independent cohorts (n= 165, n= 169) and confirmed that ASB-CLL comprises about 20 % of CLL patients. The inferior overall survival observed in ASB-CLL was independent of both TP53- and IGHV mutation status. Our multi-omics analysis refines the classification of CLL and highlights the potential of proteomics to improve cancer patient stratification beyond genetic and transcriptomic profiling. This is the transcriptomics data of the discovery cohort.
Up to now, there are two hypothesis about the pathogenesis of the relationship of intravenous leiomyomatosis and uterine myoma. One theory suggests that the IVL comes from the smooth muscle cell in the vessel wall.The other theory indicates that the IVL derives from the uterine myometrium. However, limited to the technology, few studies have been deeply explore the underlying relation. In this study, we employ the RNA sequencing to explore the molecule relationship between IVL and uterus myoma. In order to identify the molecule relationship between IVl and uterine myoma we conducted transcriptome sequencing and bioinformaitc analysis
Mice with medulloblastoma (Group 3) were treated with sham (isofluorane and imaging xray) or CSI as described by Abbas et al (2022). Total RNA was isolated with RNeasy Plus Mini Kit (Qiagen), library preparation (SureSelect, Agilent), rRNA depletion (Ribo-Zero Plus, Illumina) and sequencing were carried out by GenomicsWA or Australian Genome Research Facility. Libraries were sequenced on NovaSeq 6000 S1 flow cells as paired-end 150bp reads (Illumina).
Mice with medulloblastoma (Group 3) were treated with saline, cyclophosphamide, or gemcitabine as described by Abbas et al (2020). Total RNA was isolated with RNeasy Plus Mini Kit (Qiagen), library preparation (SureSelect, Agilent), rRNA depletion (Ribo-Zero Plus, Illumina) and sequencing were carried out by GenomicsWA or Australian Genome Research Facility. Libraries were sequenced on NovaSeq 6000 S1 flow cells as paired-end 150bp reads (Illumina).
In Vivo Loss of Tumorigenicity in a Patient-Derived Orthotopic Xenograft Mouse Model of Ependymoma. Whitehouse et al. 2023 Frontiers in Oncology. We describe the establishment of a patient-derived orthotopic xenograft (PDOX) model of posterior fossa A (PFA) EPN, derived from a metastatic cranial lesion. Patient and PDOX tumors were analyzed using RNA sequencing. WSG data (paired end) provided here correspond to germline DNA, Surgical sample 4 (described in the above manuscript as a cranial metastasis of PFA ependymoma), and a patient-derived xenograft derived from the patient.
Pilot study to set up sequencing protocols for targeted pulldown methylation profiling
Detection of BAP1 mutations in DNA from 3 uveal melanoma cell lines.
We aim to describe the transcriptomic landscape of infant spindle cell tumours.
Whole genome sequencing of immune cells from patients diagnosed with psoriatic arthritis
The aim of this study is to analyse the genomes of tumours
Sequencing data from oestrogen-receptor-alpha-positive metastatic lobular breast cancer sample
Affymetrix SNP6.0 genotype data for prostate cancer patients
Whole-exome sequencing on Illumina HiSeq2000/2500 of colorectal cancer metastasis sample (OT2_cohort)
Whole-exome sequencing on Illumina HiSeq2000/2500 of colorectal cancer primary tumor sample (OT2_cohort)
Illumina platform sequencing of whole genome libraries prepared from normal, Barrett's oesophagus and oesophageal cancer samples from 44 donors
Illumina HiSeqXTen platform sequencing data of whole genome libraries prepared from 156 matched tumour-normal samples from 78 donors
Aligned sequence data from 14 Prostate cancer samples with BRCA2 mutations
Whole-exome sequencing on Illumina HiSeq2000/2500 of colorectal cancer primary tumor sample
36 samples from individuals with colorectal tumors, whole genome sequencing
In this study, we separately performed PCR-free whole genome sequencing on the paired tumor/normal melanoma COLO-829 and lymphoblastoid COLO-829BL cell lines across three separate institutions (TGen, Illumina, Genome Sciences Centre at the British Columbia Cancer Agency). We performed a meta-analysis of all data, in combination with the originally reported analysis of these cell lines by Pleasance et al., and report a somatic reference standard based on consensus events. This standard can be used as a reference for tumor/normal whole genome analyses.
Ten patients with treatment-naïve, locally advanced or localized prostate cancer underwent radical prostatectomy. Pathological stage ranged from T2aN0 to T3bN1, and Gleason scores from 3+4 to 4+5. Tumor foci were mapped, and DNA was extracted from multiple (5-9) regions from a single, contiguous index focus. Whole exome sequencing was performed to identify single nucleotide variants and indels, and low coverage whole genome sequencing was performed to estimate copy number variation. Phylogenetic relationships between foci was determined, and alterations associated with advanced disease or response to targeted therapy were identified.
