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• HCI-PDX Trial Center for Breast Cancer Therapy

  The HCI-PDX Trial Center for Breast Cancer Therapy study is a collection of patient-tumor samples that are serially established as patient-derived tumor xenografts (human tumor in mouse) and matching organoids. For this study, we describe valuable methods and resources to generate organoids and use them as cost-effective models for precision drug screens. This study leveraged whole-exome sequencing, RNAseq, and SNP-array data to illustrate how the heterogeneity of tumors is preserved in xenograft and organoid models. Sequencing files are provided for whole-exome and RNAseq data. Processed copy number variant calls from the SNP arrays are also available. A full description of the study can be found in the article entitled, "A human breast cancer-derived xenograft and organoid platform for drug discovery and precision oncology," written by Guillen et al., 2022 in Nature Cancer (PMID: 35221336).

  Study phs002479

• UCSF Center for Reproductive Health (CRH) Research Bank

  The purpose of this study is to provide a reference profile of small extracellular RNAs in body fluids. These samples were originally obtained in a study that had a different purpose. The purpose of the original study was to add excess biological materials during the course of IVF treatment to a tissue bank. These biological materials included follicular fluid (the liquid that comes out of the ovary with the egg), granulosa cells (cells that surround the egg and help it grow), and other biological materials that help eggs, sperm, and embryos stay healthy and grow outside the body. These banked specimens would allow researchers to learn more about infertility and how to treat it, including studying how to identify the healthiest eggs, sperm, and embryos and how to help them stay healthy and grow.

  Study phs001695

• Consortium on Asthma among African-ancestry Populations in the Americas (CAAPA)

  Asthma is a complex disease where the interplay between genetic factors and environmental exposures influences susceptibility and disease prognosis. Asthmatics of African descent tend to have more severe asthma and more severe clinical symptoms than individuals of European ancestry. Advances in genetic and genomic technologies have revolutionized gene discovery for several complex diseases, but going to the next step in gene discovery for asthma among populations of African descent requires considering unique characteristics of this ethnic group, including adequate sample sizes and population stratification due to (European and African) admixture. Thus far, coverage of common genetic markers both in public databases and commercially available SNP chips has been inadequate to detect and measure genetic associations among African admixed populations. The aim of this study was therefore to catalog genetic diversity in populations of African descent, especially those whose ancestry reflects the African Diaspora in the Americas.

  Study phs001123

• Genomic Characterization CS-MATCH-0007 Arm Z1B

  The CS-MATCH-0007 protocol is part of a collaboration between the Center for Cancer Genomics (CCG) and the Division of Cancer Treatment and Diagnosis (DCTD) to perform whole-exome sequencing and RNA sequencing using pre-and post-treatment tumor biopsy specimens from patients enrolled on a treatment arm of the NCI-MATCH Clinical Trial (EAY131). The goal of this study is to identify the molecular basis for response and resistance to targeted therapies that are matched to specific genomic alterations found in their cancers. Arm Z1B is one of the treatment sub-protocols within the NCI-MATCH Clinical Trial (EAY131) where patients with CCND1, CCND2, and/or CCND3 amplifications are treated with Palbociclib. This subprotocol is one of the treatment arms included in the CS-MATCH-0007 protocol and will provide specimens for the program including DNA from tumor tissue and whole blood.

  Study phs002180

• NHLBI TOPMed: Stanford Cardiovascular Institute iPSC Biobank Study (SCVI)

  The proposed Stanford Cardiovascular Institute (SCVI) Biorepository will curate and manage an expanded collection of human induced pluripotent stem cell (iPSC) lines and provide investigators with iPSC materials generated using standardized protocols, with the overall objective of promoting the continued adoption and development of iPSC technology in cardiovascular research. Human iPSCs have revolutionized disease modeling, drug screening, and therapeutic research. However, it is also recognized that the need for specialized technical expertise and the associated cost have largely prevented individual research laboratories from adopting iPSC models in their inquiries, particularly in studies requiring multiple cell lines. To address this bottleneck, the proposed Biorepository will maintain our existing collection of iPSC lines and further expand the collection of iPSCs by recruiting 1,000 healthy, hypertrophic cardiomyopathy (HCM), dilated cardiomyopathy (DCM) donors of both sexes and diverse racial/ethnic backgrounds (African Americans, Asians, Hispanics, and Whites).

  Study phs002338

• Co-culture experiment (hashed samples)

  The principles governing tissue architecture and the mechanisms underlying its disruption in disease remain poorly understood. Here, we utilized single-cell and spatial mapping to interrogate the mechanisms directing immune cell organization in human lymph nodes and its disruption in architecturally distinct lymphoma entities: indolent follicular lymphoma (FL) and aggressive diffuse large B cell lymphoma (DLBCL). Our data substantiate the central role of lymph node stromal cells in chemokine-driven lymphocyte zonation and reveal an inflammatory feedback loop fueled by tumor-reactive T cells, triggering stromal remodeling, progressive loss of homeostatic chemokine gradients and tissue organization from non-malignant to FL and DLBCL. Loss of homeostatic chemokines was associated with adverse patient survival, identifying the underlying architectural rearrangement as a key event during lymphomagenesis. Collectively, our results highlight the principles of lymph node organization and suggest how lymphoma-induced microenvironmental reprogramming drives loss of tissue organization.

  Study EGAS50000001252

• Combination_therapies_for_personalized_cancer_medicine

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

  Study EGAS00001000655

• IYDP Indonesian Y chromosome Diversity Project

  Island Southeast Asia and Oceania host one of the world’s richest assemblages of human phenotypic, linguistic and cultural diversity. We compiled ~9.7 Mb of Y chromosome sequence from a diverse sample of over 380 men from this region, including 126 from Indonesian islands, first reported here. The granularity of this dataset allows us to fully resolve and date the regional Y chromosome phylogeny. This improved Y chromosome topology highlights localized events with important historical implications, including pre-Holocene contact between Mainland and Island Southeast Asia, ongoing interactions between Australia and the Papuan world, and a sustained period of diversification following the flooding of the ancient Sunda and Sahul continents as the insular landscape of today formed. The high-resolution phylogeny of the Y chromosome presented here thus enables a detailed exploration of past isolation, interaction and change in one of the world’s least understood regions.

  Study EGAS00001006028

• Human breast transcriptome analysis

  Obesity is a risk factor for the development of post-menopausal breast cancer and is associated with a worse breast cancer prognosis. Here we carried out transcriptome profiling on nontumorous breast tissue to define the molecular changes that occur related to excess body fat and adipose inflammation. A second goal was to determine if blood biomarkers reflect molecular changes in the breast. Increases in a variety of pathways linked to tumor development and progression were found. Moreover, increased expression of several drug targets including aromatase, the rate-limiting enzyme for estrogen biosynthesis, and PD-1 was observed. Various blood biomarkers that are associated with either elevated risk of breast cancer or worse prognosis were altered and correlated with molecular changes in the breast. Collectively, this study helps to explain both the link between obesity and breast cancer and the utility of blood biomarkers for determining risk and prognosis.

  Study EGAS00001004665

• Genomic landscape and molecularly-informed therapy in thymic carcinoma and other advanced thymic epithelial tumors (H021, HIPO)

  The molecular landscape of malignant thymic epithelial tumors (TET) is largely unknown. To better understand and target these clinically challenging entities, we characterize 81 patients harboring 46 thymus carcinomas (TC), 8 neuroendocrine tumors of the thymus (NET) and 27 thymomas using WGS/WES, transcriptome and methylome analysis. TC harbor different molecular alterations compared to thymoma and NET and have higher tumor mutational burden than thymomas. 14/76 TET patients show (likely) pathogenic germline alterations. Composite biomarker analysis indicates homologous repair deficiency in a subset of patients. We identify immunologically hot and cold TC. Cold TC show significantly shorter overall survival. 71/81 patients receive molecularly-informed therapy recommendations, which are applied in 28/71 cases leading to a DCR of 60% and an ORR of 24% (both n=25). 8/23 patients reach PFS ratios > 1.3, seven of them having TC.

  Study EGAS00001006408