Differential and limited expression of mutant alleles in multiple myeloma

Naim U. Rashid, Adam S. Sperling, Niccolo Bolli, David C. Wedge, Peter Van Loo, Yu Tzu Tai, Masood A. Shammas, Mariateresa Fulciniti, Mehmet K. Samur, Paul G. Richardson, Florence Magrangeas, Stephane Minvielle, P. Andrew Futreal, Kenneth C. Anderson, Herve Avet-Loiseau, Peter J. Campbell, Giovanni Parmigiani, Nikhil C. Munshi

Research output: Contribution to journalArticlepeer-review

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.Onaverage, 27%(range, 11%to47%)ofmutatedalleles are foundto be expressed, and among mutated genes that are expressed, there often is allele-specific expression where either the mutant or wild-type all eleissup pressed. 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.

Original languageEnglish (US)
Pages (from-to)3110-3117
Number of pages8
JournalBlood
Volume124
Issue number20
DOIs
StatePublished - Nov 13 2014
Externally publishedYes

ASJC Scopus subject areas

  • Hematology
  • Biochemistry
  • Cell Biology
  • Immunology

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