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• Plasma-Seq of patients with metastatic prostate cancer

  Study 1 In this study we analysed patients with metastatic prostate cancer to scan their tumor genomes noninvasively in plasma DNA. We wanted to make whole-genome analysis from plasma DNA amenable to clinical routine applications and developed an approach based on a benchtop high-throughput platform, i.e. Illuminas MiSeq instrument. We performed whole-genome sequencing from plasma at a shallow sequencing depth to establish a genome-wide copy number profile of the tumor at low costs within 2 days. The genome-wide profiling in the plasma of our patients revealed multiple copy number aberrations including those previously reported in prostate tumors, such as losses in 8p and gains in 8q. High-level copy number gains in the AR locus were observed in patients with CRPC but not with CSPC disease. We identified the TMPRSS2-ERG rearrangement associated 3-Mbp deletion on chromosome 21 and found corresponding fusion plasma fragments in these cases. In an index case multiregional sequencing of the primary tumor identified different copy number changes in each sector, suggesting multifocal disease. Our plasma analyses of this index case, performed 13 years after resection of the primary tumor, revealed novel chromosomal rearrangements, which were stable in serial plasma analyses over a 9 months period, which is consistent with the presence of one metastatic clone. Our approach provides specific genomic signatures within 2 days which may therefore serve as “liquid biopsy”.

  Study EGAS00001000451

• The spatio-temporal evolution of lymph node spread in early breast cancer

  Purpose: The most significant prognostic factor in early breast cancer is lymph node involvement. This stage between localised and systemic disease is key to understanding breast cancer progression, however our knowledge of the evolution of lymph node malignant invasion remains limited, as most currently available data derive from primary tumours. Experimental design: In 11 treatment-naïve node positive early breast cancer patients without clinical evidence of distant metastasis, we investigated lymph node evolution using spatial multi-region sequencing (n=78 samples) of primary and lymph node deposits and genomic profiling of matched longitudinal circulating tumour DNA (ctDNA). Results: Linear evolution from primary to lymph node was rare (1/11) whereas the majority of cases displayed either early divergence between primary and nodes (4/11), or no detectable divergence (6/11) where both primary and nodal cells belonged to a single recent expansion of a metastatic clone. Divergence of metastatic subclones was driven in part by APOBEC. Longitudinal ctDNA samples from 2 subjects taken peri-operatively reflected the two major evolutionary patterns and demonstrate that private mutations can be detected even from early metastatic nodal deposits. Moreover, node removal resulted in disappearance of private lymph node mutations in ctDNA.Conclusions: This study sheds new light on a crucial evolutionary step in the natural history of breast cancer, demonstrating early establishment of axillary lymph node metastasis in a substantial proportion of patients.

  Study EGAS00001002947

• Initial whole genome sequencing of plasma cell neoplasms in First Responders exposed to the World Trade Center attack of September 11, 2001

  The World Trade Center (WTC) attack of September 11, 2001 created an unprecedented environmental exposure to known and suspected carcinogens. High incidence of multiple myeloma (MM) and precursor conditions has been reported among first responders to the WTC disaster. To expand on our prior screening studies, and to characterize the genomic impact of the exposure to known and potential carcinogens in the WTC debris, we were motivated to perform whole genome sequencing (WGS) of WTC first responders and recovery workers who developed a plasma cell disorder after the attack. PATIENTS AND METHODS: We performed WGS of 9 CD138-positive bone marrow mononuclear samples from patients who were diagnosed with plasma cell disorders after the WTC disaster. RESULTS: No significant differences were observed in comparing the post-WTC driver and mutational signatures landscape with 110 previously published WGS from 56 patients with MM and the CoMMpass WGS cohort (n=752). Leveraging constant activity of the single base substitution mutational signatures 1 and 5 over time, we estimated that tumor-initiating chromosomal gains were windowed to both pre- and post-WTC exposure. CONCLUSIONS: Although limitations in sample size preclude any definitive conclusions, our findings suggest that the observed increased incidence of plasma cell neoplasms in this population is due to complex and heterogeneous effects of the WTC exposure that may have initiated or contributed to progression of malignancy.

  Study EGAS00001004467

• 33 patients with Monoclonal Gammopathy of Undetermined Significance (MGUS) had whole exome sequencing performed. Cells were sorted by FACSAria using CD138, CD19 and CD56 to obtain a pure abnormal plasma cell population. Generated somatic variants were compared to a previous study of 463 multiple myeloma patients.

  Monoclonal gammopathy of undetermined significance (MGUS) is a premalignant precursor of multiple myeloma (MM) with a 1% risk of progression per year. Although targeted analyses have shown the presence of specific genetic abnormalities such as IGH translocations, RB1 deletion, 1q gain, hyperdiploidy or RAS genes mutations, little is known about molecular mechanism of malignant transformation. We have performed whole exome sequencing together with SNP array analysis in 33 flow-cytometry separated abnormal PC samples of MGUS patients to describe somatic gene mutations and chromosome changes at the genome-wide level. Non-synonymous mutations (NS-SNVs) and copy number alterations (CNAs) were present in 97.0% and in 63.6% of cases, respectively. Importantly, the number of somatic mutations was significantly lower in MGUS compared to MM (p<10-4) and we have identified 6 myeloma significantly mutated genes which are KRAS, NRAS, DIS3, HIST1H1E, EGR1 and LTB in the MGUS dataset. We also found a positive correlation with increasing chromosome changes and somatic mutations. IGH translocations were present in 27.3% of cases comprising t(4;14), t(11;14), t(14;16) or t(14;20) and were in a similar frequency to MM, which corresponded with primary lesion hypothesis. Data from this study showed MGUS is a genetically comprehensive disease, however overall genetic instability is significantly lower compared to MM.

  Study EGAS00001001658

• DAC for Combined MEK and BCL-2/XL inhibition is effective in high-grade serous ovarian cancer patient-derived xenograft models and BIM levels are predictive of responsiveness

  Dac EGAC00001001250

• Cancer Genomics, ICR, summary data

  DAC for summary level data from the Cancer Genomics group, Division of Genetics and Epidemiology at the Institute of Cancer Research, Sutton, UK.

  Dac EGAC50000000050

• Picuris Pueblo Genomic Project (Modern Data)

  Data Access Committee for the present-day dataset of the project "Picuris Pueblo oral history and genomics reveal continuity in US Southwest".

  Dac EGAC50000000526

• DAC for DRS peripheral blood, University Medical Center Johannes Gutenberg University Mainz

  This DAC is in relation to the DRS samples of peripheral blood of healthy control

  Dac EGAC50000000667

• University Clinic Golnik DAC

  DAC of the University Clinic Golnik, that will decide regarding the requests for data submitted on behalf of research groups of the Clinic

  Dac EGAC50000000820

• Ontario Institute for Cancer Research; Biliary Tract Cancer

  Next Generation Sequencing data from Biliary Tract cancers

  Study EGAS50000000972

• Bulk RNA-Seq Digital Gene Expression Matrix

  Raw read counts and normalized read counts for each gene

  Dataset EGAD50000002489

• Whole Exome Sequencing Data

  This dataset includes: whole exome sequencing data for a total of 23 BCP-ALL patients - BAM files

  Dataset EGAD50000001519

• DNABR

  Genome variation data for 2723 Brazilian individuals from the DNA do Brasil Project.

  Dataset EGAD50000001012

• HMO-microbiome study dataset, 16S sequencing

  This dataset contains 16S sequencing of fecal and milk samples for HMO-microbiome Lifelines NEXT study

  Dataset EGAD50000000532

• HumanOrigins_SW_Angola

  The compressed file contains plink format files for the Affymetrix Human Origins SNP array data of 208 Angolan individuals

  Dataset EGAD00010002458

• Serum Proteomics of Aortic Diseases

  Comparative proteome-based analysis of different autologous bone entities used for alveolar onlay grafting

  Dataset EGAD00010002314

• SPGRX_genotype

  Cohort: Raw genotype files for SPGRX cohort. Genotype Chip: the Illumina Global Screening Array-24 v3.0 genomic build: b38

  Dataset EGAD00010002176

• Copy number profiling of primary samples and cell lines of retinoblastoma

  Illumina SNP-arrays for matching retinoblastoma-blood pairs and retinoblastoma cell lines.

  Dataset EGAD00010000908

• README-for-EGAS00001004349-linking-HIPO-K09R-RNA-files

  Dataset EGAD00001006785

• DATA FILES FOR SJRB

  Retinoblastoma whole genome sequencing

  Dataset EGAD00001000261

• Microsatellite unstable colorectal cancers

  Mapped data for 10 Colon MSI cancer samples

  Dataset EGAD00001004500

• PCGP ERG (WGS)

  DATA FILES FOR PCGP SJERG (WGS)

  Dataset EGAD00001002676

• PCGP ERG (WXS)

  DATA FILES FOR PCGP SJERG (WXS)

  Dataset EGAD00001002677

• RNA sequencing BRAF fusion partners

  Contains RNAseq data for 14 transduced/non-transduced organoids

  Dataset EGAD00001005380

• Long-term organoid culture of a small intestinal neuroendocrine tumor

  tissue, organoid and normal bam files for whole exome samples

  Dataset EGAD00001010162