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• Whole genome shotgun sequencing and somatic mutations data in Hepatocellular carcinoma

  Hepatocellular carcinoma (HCC) is the most common malignancy of the liver. Genomic analysis is conducted to identify genetic alterations in driver genes which are all druggable targets for cancer therapy.

  Study EGAS00001002578

• Coenzyme Q10 (CoQ) in Huntington's Disease (HD) (2CARE)

  This is a multi-center, randomized, double-blind, placebo-controlled trial of CoQ involving 609 ambulatory subjects with HD who are not requiring skilled care or institutionalization. Eligible subjects were randomized to receive either CoQ 2400 mg/day or matching placebo. Subjects were followed prospectively and systematically for 60 months of double-blind observation. The primary outcome variable is a combination of time to death (for subjects who die) and the change from baseline to Month 60 in Total Functional Capacity (TFC) score (for subjects who survive). The primary hypothesis of the study is that chronic treatment of early-stage HD subjects with high-dosage CoQ will slow the progressive functional decline of HD.

  Study phs001065

• GWAS for Genetic Determinants of Bone Fragility in European-American Premenopausal Women

  Osteoporotic fractures are largely due to an increased propensity to fall with aging and a reduction in bone strength. Although skeletal architecture contributes to fracture risk, bone mineral density (BMD) is the most important determinant of bone strength and fracture risk. Between 60 and 80% of the variance of BMD of adult Caucasian women is due to heritable factors. Final BMD is a function of peak bone mass attained during young adulthood and the subsequent rate of bone loss, which occurs as a result of both post-menopausal estrogen loss and aging. The evidence for a genetic contribution to rate of loss in BMD is substantially weaker than that for peak BMD. Therefore, we have focused our sample collection on the recruitment of premenopausal women, in whom we have sought to identify the genes influencing peak BMD at the spine and hip, the two major skeletal sites of osteoporotic fracture. The primary goal of this study is to identify genes that affect peak BMD in premenopausal women. Identification of these genes may: 1) lead to molecular tests that predict risk of osteoporosis and allow institution of early preventive measures; 2) provide insight into basic bone cell biology and other factors that affect peak BMD; and 3) provide molecular targets for therapeutic agents to increase BMD.

  Study phs000138

• NHLBI TOPMed: Genetic Epidemiology of COPD (COPDGene)

  Chronic obstructive pulmonary disease (COPD) is the fourth leading cause of death in the United States, and the only leading cause of death that is steadily increasing in frequency. This project established a racially diverse cohort that is sufficiently large and appropriately designed for genome-wide association analysis of COPD. A total of 10,720 subjects were recruited, including control smokers and nonsmokers, definite COPD cases (GOLD Stage 2 to 4), and subjects not included in either group (GOLD 1 and PRISm). This cohort is being used for cross-sectional analysis, and long-term longitudinal follow-up visits after five years and after ten years are also being performed. The primary focus of the study is to identify the genetic risk factors that determine susceptibility for COPD and COPD-related phenotypes. Detailed phenotyping of both cases and controls, including chest CT scan assessment of emphysema and airway disease, will allow identification of genetic determinants for the heterogeneous components of the COPD syndrome. The aims for this study are: Precise phenotypic characterization of COPD subjects using computed tomography, as well as clinical and physiological measures, that will provide data to enable the broad COPD syndrome to be decomposed into clinically significant subtype; Genome-wide association studies will identify genetic determinants for COPD susceptibility that will provide insight into clinically relevant COPD subtypes; Distinct genetic determinants influence the development of emphysema and airway disease. The TOPMed analysis will include approximately 10,500 subjects with whole genome sequencing after quality control is completed. Comprehensive phenotypic data for COPDGene subjects is available through dbGaP study phs000179.

  Study phs000951

• Next_gen_seq_of_eye_cancers

  Retinoblastoma (RB), the commonest eye cancer in children was the first cancer for which a genetic cause was identified: the Rb1 gene is a tumour suppressor gene that is mutated in RB. The Rb1 gene defect alone does not predict the clinical outcome. We propose to study other possible mechanisms: 1. Stepwise further mutations occur in RB, increasing its carcinogenesis. We will sequence the whole genome in RB tissue, and relate the different genes expressed to the treatments used. 2. Extracellular matric proteins contribute to a tumour permissive environment for RB to continue to grow. This includes Samll Leucine Rich Proteoglycans (SLRP), a family of 15 secreted extracellular matrix proteins involved in eye development. 3. Cancer stem cells (CSC), a subpopulation of treatment resistant cells, drive RB tumours, and whether these stem cells can be manipulated for new therapies. The aim of this study is to assist finding targeted diagnostic techniques and treatments for RB.

  Study EGAS00001002309

• Anaplastic_Meningioma_WGS_X10

  Anaplastic meningiomas are a rare, malignant variant of meningioma. At present there is no effective treatment for this cancer. The aim of the study is to identify somatic mutations in anaplastic meningiomas. We plan to sequence a set of 500 known cancer genes in 50 anaplastic meningioma and corresponding peripheral blood DNA samples. Bioinformatics will be used to analyse the results to assess the probability of these mutations being causal and so likely of critical importance for the tumour growth. Identification of these mutations will guide selection of appropriate compounds to effectively treat the disease.

  Study EGAS00001000859

• WES sequencing of metastatic colorectal cancer patient-derived xenografts with known response to irinotecan.

  Chemotherapy is the standard-of-care treatment for metastatic colorectal cancer (mCRC) and benefits some patients, but what distinguishes responders from non-responders is unclear. In this study, we expand a pre-existing collection (https://doi.org/10.1158/2159-8290.CD-24-0556) of molecularly annotated patient-derived xenografts to uncover functional predictors of response to 5-FU and irinotecan combination therapy (FOLFIRI) in mCRC. We complemented previous mutational profiles with whole exome sequencing for 46 xenografts with known response to irinotecan.

  Study EGAS50000001484

• Bulk RNA sequencing of metastatic colorectal cancer patient-derived xenografts with known response to irinotecan

  Chemotherapy is the standard-of-care treatment for metastatic colorectal cancer (mCRC) and benefits some patients, but what distinguishes responders from non-responders is unclear. In this study, we expand a pre-existing collection (https://doi.org/10.1158/2159-8290.CD-24-0556) of molecularly annotated patient-derived xenografts to uncover functional predictors of response to 5-FU and irinotecan combination therapy (FOLFIRI) in mCRC. We complemented previous expression profiles with bulk RNAseq for 38 xenografts with known response to irinotecan.

  Study EGAS50000001485

• Immune Biomarkers in Metastatic Castration-resistant Prostate Cancer

  Background: Metastatic castration-resistant prostate cancer (mCRPC) is a heterogeneous disease in which molecular stratification is needed to improve clinical outcomes. The identification of predictive biomarkers can have a major impact on the care of these patients, but the availability of metastatic tissue samples for research in this setting is limited. Objective: To study the prevalence of immune biomarkers of potential clinical utility to immunotherapy in mCRPC by tumour RNA sequencing, and to determine their association with overall survival (OS).

  Study EGAS50000001269

• NCI Cancer Model Development for the Human Cancer Model Initiative (HCMI)

  The Cancer Model Development Center (CMDC) project is part of the Human Cancer Model Initiative (HCMI) and is managed by the Office of Cancer Genomics within the Center for Cancer Genomics at the National Cancer Institute (NCI). The goal of the HCMI is to generate approximately 1000 novel human "next generation" tumor-derived models as a community resource. The models aim to faithfully recapitulate the cellular complexity and heterogeneity of human tumors. The CMDCs are tasked by the NCI with producing a proportion of the cancer models. Wellcome Sanger Institute (WSI) is a contributing member of the HCMI. Models developed by HCMI are being derived from a number of tumor types and subtypes (see below), including rare adult, pediatric and understudied cancers. The number of models and the clinical sites from which patient samples are acquired is increasing. Normal tissue, originating tumor, and tumor-derived models are sequenced. The next generation cancer models are associated with rich clinical and genomic data through the NCI Genomic Data Commons for all researchers to advance cancer research. The CMDC and HCMI models will serve as excellent tools in research to provide insight into the pathways that influence tumor growth and progression, how tumors respond to therapy, etc. Ultimately, the data generated using these models will support the development of personalized oncology. There is a delay between registered IDs and model availability. The current model count is found in The HCMI Searchable Catalog which is updated when new models are available for distribution to the research community.

  Study phs001486