Initial genome sequencing and analysis of multiple myeloma

By M. Chapman, M. Lawrence, J. Keats, Kristian Cibulskis, C. Sougnez, Anna C. Schinzel, C. Harview, Jean-Philippe Brunet, G. Ahmann, Mazhar Adli and 39 more. Nature, 2011

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Multiple myeloma is an incurable malignancy of plasma cells, and its pathogenesis is poorly understood. Here we report the massively parallel sequencing of 38 tumour genomes and their comparison to matched normal DNAs. Several new and unexpected oncogenic mechanisms were suggested by the pattern of somatic mutation across the data set. These include the mutation of genes involved in protein translation (seen in nearly half of the patients), genes involved in histone methylation, and genes involved in blood coagulation. In addition, a broader than anticipated role of NF-κB signalling was indicated by mutations in 11 members of the NF-κB pathway. Of potential immediate clinical relevance, activating mutations of the kinase BRAF were observed in 4% of patients, suggesting the evaluation of BRAF inhibitors in multiple myeloma clinical trials. These results indicate that cancer genome sequencing of large collections of samples will yield new insights into cancer not anticipated by existing knowledge.

Subfields: Hematology, Molecular Biology

View Paper: https://www.semanticscholar.org/paper/271d2d50b2124faa0f4dab1c695066ffe14f3163

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Citations in the corpus

A Landscape of Driver Mutations in Melanoma (2012, methodology): “Pioneering studies have led to increasing appreciation of the confounding effects of variable regional basal mutation rates, motivating refinements such as gene-specific basal mutation rate calculations based on synonymous mutations, binning genes based on expression levels to correct for correlatio”
Scalable Open Science Approach for Mutation Calling of Tumor Exomes Using Multiple Genomic Pipelines (2018, neutral): “For analyses in this manuscript we restricted Indelocator calls to indels depth of greater than or equal to 3 supporting alternate reads.”
Integrative and comparative genomic analysis of HPV-positive and HPV-negative head and neck squamous cell carcinomas (2014, methodology): “We applied the MutSig method to identify cancer-relevant genes demonstrating evidence of statistical selection for mutations in our cohort (20-22, 27).”
Mutational heterogeneity in cancer and the search for new cancer genes (2013, neutral): “(6) regression version of MutSigCV (“with covariates”), where three gene characteristics (expression level, DNA replication time, and HiC chromatin compartment, Table S5) were used in a multivariate linear regression (Table S6) to predict the genespecific mutation frequency.”
The Life History of 21 Breast Cancers (2012, background): “Whole-cancer genomes sequenced to date carry thousands to tens of thousands of somatic mutations (Chapman et al., 2011; Ding et al., 2010; Ley et al., 2010; Pleasance et al., 2010a, 2010b; Puente et al., 2011; Shah et al., 2009), the vast majority of which probably have no biological relevance.”