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• Comprehensive Genomic Characterization of Refractory Multiple Myeloma Reveals a Complex Mutational and Structural Landscape Associated with Drug Resistance (H067)

  Outcome of patients with multiple myeloma (MM) refractory to immunomodulatory agents (IMiDs) and proteasome inhibitors (PIs) is still very poor. To elucidate the genetic landscape of relapsed/refractory MM (RRMM) we performed whole genome and transcriptome sequencing of 39 heavily pretreated RRMM patients with at least double refractoriness revealing complex structural changes and a high mutational load (H067/K08K). We found a median of 67 structural variants and 116 nonsynonymous exonic mutations per patient. Assessment of oncogenic drivers showed NRAS, BRAF, TP53, KRAS, SLC4A7, FAM46C, DIS3, RB1, KMT2C, MLLT4, EWSR1, HCFC2, and COPS3 as significantly mutated. We found multiple genomic regions with bi-allelic events affecting known tumor suppressor genes, most frequently TP53, RB1, and TRAF3. Supervised analysis of mutational signatures showed a major contribution of Cosmic signature 6 associated with deficiency in DNA mismatch repair and the ‘BRCAness’ signature which coincided with mutations in genes known to confer PARP inhibitor sensitivity. Recurrently mutated gene networks included genes with relevance for PI and IMiD activity, the latter including in particular members of the Cereblon and the COP9 signalosome complex. In conclusion, this comprehensive genomic characterization revealed a complex mutational and structural landscape in RRMM and highlights potential implications for therapeutic strategies.

  Study EGAS00001004363

• Sequencing data (BAM files) from - A mutation in VPS15 (PIK3R4) causes a ciliopathy and affects IFT20 release from the cis-Golgi. The Data Access Committee (DAC) is responsible for sequencing data release to external requestors based on consent and/or National Research Ethics terms.

  Dac EGAC00001000552

• Metagenome shotgun sequencing of the Inflammatory Bowel Disease

  We performed a comprehensive metagenome-wide association study for inflammatory bowel disease by utilizing whole-genome shotgun sequencing.

  Study JGAS000530

• WTCCC2 Pharmacogenomic Response to Statins study

  A WTCCC2 project genome-wide study for pharmacogenomic response to statins (PR) in individuals from Scotland.

  Study EGAS00000000121

• KIT-dependent and -independent genomic heterogeneity of resistance in gastrointestinal stromal tumors - TORC1/2 inhibition as salvage strategy

  The mutational status of GIST analyzed with a broad sequencing approach (WES, RNAseq)

  Study EGAS00001003405

• McQuillin_Global_WES_Schizophrenia

  Whole Exome Sequencing of Schizophrenia cases and matched controls performed at the Broad Institute on a cohort from UCL, London, UK

  Study EGAS50000000901

• ICGC Breast Cancer Project

  A comprehensive characterisation and analysis of human breast cancers through genome-wide approaches including genomics, transcriptomics and epigenomics.

  Study EGAS00001001195

• WTCCC2 BO (Barretts oesophagus) samples

  A WTCCC2 project genome-wide case-control association study for Barretts oesophagus in individuals from the UK.

  Study EGAS00001000628

• Metastatic_breast_cancer_targeted_gene_screen

  The samples will be sequenced for a targeted panel of cancer relevant genes (n ~ 370) and analysed for somatic mutations.

  Study EGAS00001000704

• GermCellTumour

  DNA and RNA sequencing across a number of different germ cell tumours, included mixed components within the same tumour.

  Study EGAS00001003457