Initial genome sequencing and analysis of multiple myeloma

Abstract

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.

Keywords

Affiliated Institutions

• Ann Arbor Center for Independent Living US
• Mayo Clinic US
• University of Chicago US
• Translational Genomics Research Institute US
• Catholic Medical Center US
• City Of Hope National Medical Center US
• Massachusetts Institute of Technology US
• University of Michigan US
• The Ohio State University US
• Emory University US
• Dana-Farber Cancer Institute US
• Broad Institute US
• Howard Hughes Medical Institute US
• Rutgers, The State University of New Jersey US
• Washington University in St. Louis US
• Harvard University Press US
• WinnMed US
• Multiple Myeloma Research Foundation US
• Weizmann Institute of Science IL

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