title: Differential and limited expression of mutant alleles in multiple myeloma.
abstract: Recent work has delineated mutational profiles in multiple myeloma and reported a median of 52 mutations per patient, as well as a set of commonly mutated genes across multiple patients. In this study, we have used deep sequencing of RNA from a subset of these patients to evaluate the proportion of expressed mutations. We find that the majority of previously identified mutations occur within genes with very low or no detectable expression. On average, 27% (range, 11% to 47%) of mutated alleles are found to be expressed, and among mutated genes that are expressed, there often is allele-specific expression where either the mutant or wild-type allele is suppressed. Even in the absence of an overall change in gene expression, the presence of differential allelic expression within malignant cells highlights the important contribution of RNA-sequencing in identifying clinically significant mutational changes relevant to our understanding of myeloma biology and also for therapeutic applications.
authors.affiliation: Jerome Lipper Multiple Myeloma Center, Department of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA; Department of Biostatistics, Dana-Farber Cancer Institute and Harvard School of Public Health, Boston, MA;
authors.forename: Naim U
authors.initials: NU
authors.lastname: Rashid
authors.affiliation: Jerome Lipper Multiple Myeloma Center, Department of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA;
authors.forename: Adam S
authors.initials: AS
authors.lastname: Sperling
authors.affiliation: Department of Cancer Genetics and Genomics, Cancer Genome Project, Wellcome Trust Sanger Institute, Hinxton, United Kingdom; Department of Haematology, University of Cambridge, Cambridge Institute for Medical Research, Cambridge, United Kingdom;
authors.forename: Niccolo
authors.initials: N
authors.lastname: Bolli
authors.affiliation: Department of Cancer Genetics and Genomics, Cancer Genome Project, Wellcome Trust Sanger Institute, Hinxton, United Kingdom;
authors.forename: David C
authors.initials: DC
authors.lastname: Wedge
authors.affiliation: Department of Cancer Genetics and Genomics, Cancer Genome Project, Wellcome Trust Sanger Institute, Hinxton, United Kingdom; Department of Human Genetics, Vlaams Instituut voor Biotechnologie and University of Leuven, Leuven, Belgium;
authors.forename: Peter
authors.initials: P
authors.lastname: Van Loo
authors.affiliation: Jerome Lipper Multiple Myeloma Center, Department of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA;
authors.forename: Yu-Tzu
authors.initials: YT
authors.lastname: Tai
authors.affiliation: Jerome Lipper Multiple Myeloma Center, Department of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA; Department of Hematology/Oncology, Boston Veterans Administration Healthcare System, West Roxbury, MA;
authors.forename: Masood A
authors.initials: MA
authors.lastname: Shammas
authors.affiliation: Jerome Lipper Multiple Myeloma Center, Department of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA;
authors.forename: Mariateresa
authors.initials: M
authors.lastname: Fulciniti
authors.affiliation: Jerome Lipper Multiple Myeloma Center, Department of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA; Department of Biostatistics, Dana-Farber Cancer Institute and Harvard School of Public Health, Boston, MA;
authors.forename: Mehmet K
authors.initials: MK
authors.lastname: Samur
authors.affiliation: Jerome Lipper Multiple Myeloma Center, Department of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA;
authors.forename: Paul G
authors.initials: PG
authors.lastname: Richardson
authors.affiliation: Hematology Department, Centre de Recherche en Cancérologie Nantes-Angers Unité Mixte de Recherche INSERM 892-Centre National de la Recherche Scientifique 6299 and Institut de Recherche Thérapeutique de l'Université de Nantes, Nantes, France;
authors.forename: Florence
authors.initials: F
authors.lastname: Magrangeas
authors.affiliation: Hematology Department, Centre de Recherche en Cancérologie Nantes-Angers Unité Mixte de Recherche INSERM 892-Centre National de la Recherche Scientifique 6299 and Institut de Recherche Thérapeutique de l'Université de Nantes, Nantes, France;
authors.forename: Stephane
authors.initials: S
authors.lastname: Minvielle
authors.affiliation: Department of Genomic Medicine, MD Anderson Cancer Center, Houston, TX;
authors.forename: P Andrew
authors.initials: PA
authors.lastname: Futreal
authors.affiliation: Jerome Lipper Multiple Myeloma Center, Department of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA;
authors.forename: Kenneth C
authors.initials: KC
authors.lastname: Anderson
authors.affiliation: Unité de Génomique du Myélome, Centre Hospitalier Universitaire Rangueil, Toulouse, France; and Centre de Recherche en Cancérologie de Toulouse, INSERM U1037, Toulouse, France.
authors.forename: Herve
authors.initials: H
authors.lastname: Avet-Loiseau
authors.affiliation: Department of Cancer Genetics and Genomics, Cancer Genome Project, Wellcome Trust Sanger Institute, Hinxton, United Kingdom; Department of Haematology, University of Cambridge, Cambridge Institute for Medical Research, Cambridge, United Kingdom;
authors.forename: Peter J
authors.initials: PJ
authors.lastname: Campbell
authors.affiliation: Department of Biostatistics, Dana-Farber Cancer Institute and Harvard School of Public Health, Boston, MA;
authors.forename: Giovanni
authors.initials: G
authors.lastname: Parmigiani
authors.affiliation: Jerome Lipper Multiple Myeloma Center, Department of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA; Department of Hematology/Oncology, Boston Veterans Administration Healthcare System, West Roxbury, MA;
authors.forename: Nikhil C
authors.initials: NC
authors.lastname: Munshi
mesh_terms: D000483:Alleles; D004247:DNA / Q000235:genetics; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D009101:Multiple Myeloma / Q000235:genetics*; D009154:Mutation; D012313:RNA / Q000235:genetics; D017423:Sequence Analysis, RNA
chemical_list: D012313:RNA; D004247:DNA