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.
|Titolo:||Differential and limited expression of mutant alleles in multiple myeloma|
|Parole Chiave:||alleles; DNA; humans; multiple myeloma; RNA; sequence analysis, RNA; gene expression regulation, neoplastic; mutation; hematology; biochemistry; cell biology; immunology|
|Settore Scientifico Disciplinare:||Settore MED/15 - Malattie del Sangue|
|Data di pubblicazione:||2014|
|Digital Object Identifier (DOI):||10.1182/blood-2014-04-569327|
|Appare nelle tipologie:||01 - Articolo su periodico|