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Nature DOI:10.1038/nature09837

Initial genome sequencing and analysis of multiple myeloma.

Publication TypeJournal Article
Year of Publication2011
AuthorsChapman, MA, Lawrence, MS, Keats, JJ, Cibulskis, K, Sougnez, C, Schinzel, AC, Harview, CL, Brunet, JP, Ahmann, GJ, Adli, M, Anderson, KC, Ardlie, KG, Auclair, D, Baker, A, Bergsagel, PL, Bernstein, BE, Drier, Y, Fonseca, R, Gabriel, SB, Hofmeister, CC, Jagannath, S, Jakubowiak, AJ, Krishnan, A, Levy, J, Liefeld, T, Lonial, S, Mahan, S, Mfuko, B, Monti, S, Perkins, LM, Onofrio, R, Pugh, TJ, Rajkumar, SV, Ramos, AH, Siegel, DS, Sivachenko, A, Stewart, AK, Trudel, S, Vij, R, Voet, D, Winckler, W, Zimmerman, T, Carpten, J, Trent, J, Hahn, WC, Garraway, LA, Meyerson, M, Lander, ES, Getz, G, Golub, TR
JournalNature
Volume471
Issue7339
Pages467-72
Date Published2011/03/24
ISSN0028-0836
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.

URLhttp://dx.doi.org/10.1038/nature09837
DOI10.1038/nature09837
Pubmed

http://www.ncbi.nlm.nih.gov/pubmed/21430775?dopt=Abstract