Differential and limited expression of mutant alleles in multiple myeloma
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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 MunshiAbstract
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.
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Publisher website (DOI) 10.1182/blood-2014-04-569327
Europe PubMed Central 25237203
Pubmed 25237203
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