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• Clonal relationships of ductal carcinoma in situ and recurrent invasive breast cancers defined by genomic analysis

  Ductal Carcinoma In Situ (DCIS) is the most common form of pre-invasive breast cancer and despite treatment a small fraction (5-10%) of DCIS patients present with invasive disease many years later. A fundamental biologic question is whether the invasive disease recurring in the same breast is established by tumor cells in the initial DCIS or represents new unrelated disease. To address this question, we performed genomic analyses on the initial pure DCIS lesion and paired invasive recurrent tumors in 95 patients together with single cell DNA sequencing in a subset of cases. Our data shows that in 75% the invasive recurrence was clonally related to the initial DCIS, suggesting that the tumor cells were not eliminated during the initial treatment with surgery +/- radiotherapy. Surprisingly however, 18% were clonally unrelated to the DCIS, representing new independent lineages, and 7% of cases were ambiguous. Our findings show that although DCIS is often the precursor of invasive recurrence, a significant fraction of invasive recurrences are unrelated to the initial DCIS. This knowledge is essential for accurate risk evaluation of DCIS treatment de-escalation strategies and the identification of predictive biomarkers.

  Study EGAS00001005784

• Clonal relationships of ductal carcinoma in situ and recurrent invasive breast cancers defined by genomic analysis

  Ductal Carcinoma In Situ (DCIS) is the most common form of pre-invasive breast cancer and despite treatment a small fraction (5-10%) of DCIS patients present with invasive disease many years later. A fundamental biologic question is whether the invasive disease recurring in the same breast is established by tumor cells in the initial DCIS or represents new unrelated disease. To address this question, we performed genomic analyses on the initial pure DCIS lesion and paired invasive recurrent tumors in 95 patients together with single cell DNA sequencing in a subset of cases. Our data shows that in 75% the invasive recurrence was clonally related to the initial DCIS, suggesting that the tumor cells were not eliminated during the initial treatment with surgery +/- radiotherapy. Surprisingly however, 18% were clonally unrelated to the DCIS, representing new independent lineages, and 7% of cases were ambiguous. Our findings show that although DCIS is often the precursor of invasive recurrence, a significant fraction of invasive recurrences are unrelated to the initial DCIS. This knowledge is essential for accurate risk evaluation of DCIS treatment de-escalation strategies and the identification of predictive biomarkers.

  Study EGAS00001006306

• International Multiple Sclerosis Genomics Consortium (IMSGC) Genome Wide Association Study of Multiple Sclerosis

  The goal of this study is to perform a comprehensive allelic and genotypic association analysis of the entire human genome in multiple sclerosis. The recent definitive linkage genome screen demonstrated that there is no other MS risk gene with an effect size anywhere near that of the MHC. However, linkage analysis is significantly hampered by reduced power in the face of heterogeneity and requires multiplex families, which also hampers acquiring an appropriate sample size. In contrast, genotyping 500K SNPs allows us to survey a significant amount of the genome (we estimate >70%) directly for allelic or genotypic association. This uses the improved power of association analysis and can also take advantage of the linkage disequilibrium relationships among SNPs to further increase power (e.g. haplotype analysis). Quality control and data analysis are significant challenges. We will initially perform substantial QC checks and analyze the data using both TDT and AFBAC approaches. Multigenic interactions will also be tested using MDR.

  Study phs000139

• Deep Sequencing Studies for Cannabis and Stimulant Dependence

  Cannabis and stimulants are among the most widely used illicit drug in the United States, and their use is associated with substantial physical and psychiatric sequelae. Twin studies have shown a substantial genetic component to the etiology of cannabis and stimulant use disorders, but, genome-wide association studies using genotype data obtained from microarrays have yielded few robust results. The advent of increasingly economical whole genome sequencing provides new opportunities to identify trait-associated sequence variations. The present study proposes to identify sequence variants that affect stimulant and cannabis dependence in three cohorts. The three study cohorts were ascertained as part of the Mission Indian Study (PI Cindy Ehlers), the combined Yale-University of Connecticut Addiction Study samples (PI Joel Gelernter) and the San Francisco Family Study (PI Kirk Wilhelmsen). Because three populations with different continental origins were studied, the present study will also ascertain whether the major genetic risk factors for the traits of interest are shared or population-specific.

  Study phs001458

• DAC for study CMMRD–associated high-grade glioma

  This Data Access Committee (DAC) is responsible for de-identified, summarized somatic variant call data derived from paired tumor–blood Whole-exome sequencing of human samples in a glioma research study. Access requests are approved without additional restrictions and are granted solely for health-related research purposes.

  Dac EGAC50000000855

• Mitochondrial DNA sequencing of human iPSC, parental cells, and iPSC derived cardiomyocytes

  Dataset contains whole mitochondrial DNA sequencing data in fastq format (Illumina MiSeq paired-end) of 62 samples, in total. Those samples include sequencing data of the endothelial cell populations of 10 different donors and of 26 early-passage iPSC clones derived thereof. Moreover, the dataset contains the data of 7 of those iPSC clones sequenced additionally in passage 30 and 50, each. Lastly, 4 iPSC clones were sequenced during directed cardiomyocyte differentiation, each at day 0, 5, and 15 of differentiation.

  Dataset EGAD00001008021

• Gabriella Miller Kids First Pediatric Research Program in Genetics at the Intersection of Childhood Cancer and Birth Defects

  The Gabriella Miller Kids First Pediatric Research Program (Kids First) is a trans-NIH effort initiated in response to the 2014 Gabriella Miller Kids First Research Act and supported by the NIH Common Fund. This program focuses on gene discovery in pediatric cancers and structural birth defects and the development of the Gabriella Miller Kids First Pediatric Data Resource (Kids First Data Resource). All of the WGS and phenotypic data from this study are accessible through dbGaP and kidsfirstdrc.org, where other Kids First datasets can also be accessed. Birth defects and childhood cancer share biological pathways that are important for cell growth and division. We propose that sequencing pediatric patients suffering both conditions will allow us to discover the underlying genes and in turn advance our understanding of the causes of these devastating diseases.

  Study phs001846

• Whole Exome Sequencing of paired gDNAs and PPGL tumor DNA from patients with cyanotic congenital heart disease

  Fastq files from Whole Exome Sequencing of 12 paired germline DNA (from blood/saliva) and 14 PPGL tumor DNA (from formalin-fixed paraffin-embedded (FFPE) blocks from surgery) from patients with cyanotic congenital heart disease (CCHD) and pheochromocytoma and paraganglioma (PPGL). Sequencing was performed using the Illumina HiSeq4000.

  Dataset EGAD50000001201

• Whole Genome Sequencing of Therapy-Related Myeloid Neoplasms

  The dataset consists of: 51 paired tumor/normal WGS samples (26 tumors and 25 normals), and 13 normal targeted samples.

  Dataset EGAD00001010026

• The Longevity Genes Project

  Aging is a complex, universal condition leading to the functional decline of all cells and organisms, and to major national and global public health problems. Although aging is the major risk factor for developing most adult-onset diseases, systematic investigations into the fundamental physiology, biology and genetics of aging are only just beginning. In the Longevity Genes Project at Albert Einstein College of Medicine, Dr. Nir Barzilai and his team conducted genetic research on more than 500 healthy elderly people between the ages of 95 and 112, and on their children. The identification of longevity genes by Einstein researchers could lead to new drug therapies that might help people live longer, healthier lives and avoid or significantly delay age-related diseases such as Alzheimer's disease, type 2 diabetes and cardiovascular disease.

  Study phs000584