title: 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.
authors: The Eli and Edythe L. Broad Institute, 7 Cambridge Center, Cambridge, Massachusetts 02412, USA.
authors: Michael A
authors: MA
authors: Chapman
authors: Michael S
authors: MS
authors: Lawrence
authors: Jonathan J
authors: JJ
authors: Keats
authors: Kristian
authors: K
authors: Cibulskis
authors: Carrie
authors: C
authors: Sougnez
authors: Anna C
authors: AC
authors: Schinzel
authors: Christina L
authors: CL
authors: Harview
authors: Jean-Philippe
authors: JP
authors: Brunet
authors: Gregory J
authors: GJ
authors: Ahmann
authors: Mazhar
authors: M
authors: Adli
authors: Kenneth C
authors: KC
authors: Anderson
authors: Kristin G
authors: KG
authors: Ardlie
authors: Daniel
authors: D
authors: Auclair
authors: Angela
authors: A
authors: Baker
authors: P Leif
authors: PL
authors: Bergsagel
authors: Bradley E
authors: BE
authors: Bernstein
authors: Yotam
authors: Y
authors: Drier
authors: Rafael
authors: R
authors: Fonseca
authors: Stacey B
authors: SB
authors: Gabriel
authors: Craig C
authors: CC
authors: Hofmeister
authors: Sundar
authors: S
authors: Jagannath
authors: Andrzej J
authors: AJ
authors: Jakubowiak
authors: Amrita
authors: A
authors: Krishnan
authors: Joan
authors: J
authors: Levy
authors: Ted
authors: T
authors: Liefeld
authors: Sagar
authors: S
authors: Lonial
authors: Scott
authors: S
authors: Mahan
authors: Bunmi
authors: B
authors: Mfuko
authors: Stefano
authors: S
authors: Monti
authors: Louise M
authors: LM
authors: Perkins
authors: Robb
authors: R
authors: Onofrio
authors: Trevor J
authors: TJ
authors: Pugh
authors: S Vincent
authors: SV
authors: Rajkumar
authors: Alex H
authors: AH
authors: Ramos
authors: David S
authors: DS
authors: Siegel
authors: Andrey
authors: A
authors: Sivachenko
authors: A Keith
authors: AK
authors: Stewart
authors: Suzanne
authors: S
authors: Trudel
authors: Ravi
authors: R
authors: Vij
authors: Douglas
authors: D
authors: Voet
authors: Wendy
authors: W
authors: Winckler
authors: Todd
authors: T
authors: Zimmerman
authors: John
authors: J
authors: Carpten
authors: Jeff
authors: J
authors: Trent
authors: William C
authors: WC
authors: Hahn
authors: Levi A
authors: LA
authors: Garraway
authors: Matthew
authors: M
authors: Meyerson
authors: Eric S
authors: ES
authors: Lander
authors: Gad
authors: G
authors: Getz
authors: Todd R
authors: TR
authors: Golub
mesh_terms: D000595:Amino Acid Sequence; D001777:Blood Coagulation / Q000235:genetics; D018899:CpG Islands / Q000235:genetics; D004252:DNA Mutational Analysis; D004260:DNA Repair / Q000235:genetics; D005091:Exons / Q000235:genetics; D063326:Exosome Multienzyme Ribonuclease Complex; D015894:Genome, Human / Q000235:genetics*; D023281:Genomics; D006657:Histones / Q000378:metabolism; D018398:Homeodomain Proteins / Q000235:genetics; D006706:Homeostasis / Q000235:genetics; D006801:Humans; D008745:Methylation; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009101:Multiple Myeloma / Q000188:drug therapy / Q000201:enzymology / Q000235:genetics* / Q000378:metabolism; D009154:Mutation / Q000235:genetics*; D016328:NF-kappa B / Q000378:metabolism; D009857:Oncogenes / Q000235:genetics; D016366:Open Reading Frames / Q000235:genetics; D014176:Protein Biosynthesis / Q000235:genetics; D011487:Protein Conformation; D048493:Proto-Oncogene Proteins B-raf / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D012323:RNA Processing, Post-Transcriptional / Q000235:genetics; D012260:Ribonucleases / Q000737:chemistry / Q000235:genetics; D015398:Signal Transduction / Q000235:genetics; D014158:Transcription, Genetic / Q000235:genetics
chemical_list: D006657:Histones; D018398:Homeodomain Proteins; D016328:NF-kappa B; C097899:homeobox protein HOXA9; C482119:BRAF protein, human; D048493:Proto-Oncogene Proteins B-raf; D063326:Exosome Multienzyme Ribonuclease Complex; D012260:Ribonucleases; C551543:DIS3 protein, human