Chapman MA, Lawrence MS, Keats JJ, Cibulskis K, Sougnez C, Schinzel AC, Harview CL, Brunet JP, Ahmann GJ, Adli M, et al. Initial genome sequencing and analysis of multiple myeloma. Nature. 2011;471:467–72.
NOTES
Chapman, Michael ALawrence, Michael SKeats, Jonathan JCibulskis, KristianSougnez, CarrieSchinzel, Anna CHarview, Christina LBrunet, Jean-PhilippeAhmann, Gregory JAdli, MazharAnderson, Kenneth CArdlie, Kristin GAuclair, DanielBaker, AngelaBergsagel, P LeifBernstein, Bradley EDrier, YotamFonseca, RafaelGabriel, Stacey BHofmeister, Craig CJagannath, SundarJakubowiak, Andrzej JKrishnan, AmritaLevy, JoanLiefeld, TedLonial, SagarMahan, ScottMfuko, BunmiMonti, StefanoPerkins, Louise MOnofrio, RobbPugh, Trevor JRajkumar, S VincentRamos, Alex HSiegel, David SSivachenko, AndreyStewart, A KeithTrudel, SuzanneVij, RaviVoet, DouglasWinckler, WendyZimmerman, ToddCarpten, JohnTrent, JeffHahn, William CGarraway, Levi AMeyerson, MatthewLander, Eric SGetz, GadGolub, Todd RengR01 CA133115/CA/NCI NIH HHS/U54 HG003067/HG/NHGRI NIH HHS/R01 AG020686-07/AG/NIA NIH HHS/R01 AG020686/AG/NIA NIH HHS/R01 CA133115-04/CA/NCI NIH HHS/R01 CA133966-03/CA/NCI NIH HHS/K12 CA133250/CA/NCI NIH HHS/R01 CA133966/CA/NCI NIH HHS/Research Support, Non-U.S. Gov'tEnglandNature. 2011 Mar 24;471(7339):467-72. doi: 10.1038/nature09837.
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-kappaB signalling was indicated by mutations in 11 members of the NF-kappaB 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.
Last updated on 02/17/2021