Scientific Publications

Widespread genetic heterogeneity in multiple myeloma: implications for targeted therapy.

Publication TypeJournal Article
AuthorsLohr, JG, Stojanov P., Carter SL, Cruz-Gordillo P., Lawrence MS, Auclair D., Sougnez C., Knoechel B., Gould J., Saksena G., Cibulskis K., McKenna A., Chapman MA, Straussman R., Levy J., Perkins LM, Keats JJ, Schumacher SE, Rosenberg M., Multiple Myeloma Research Consortium, Getz G., and Golub T. R.
AbstractWe performed massively parallel sequencing of paired tumor/normal samples from 203 multiple myeloma (MM) patients and identified significantly mutated genes and copy number alterations and discovered putative tumor suppressor genes by determining homozygous deletions and loss of heterozygosity. We observed frequent mutations in KRAS (particularly in previously treated patients), NRAS, BRAF, FAM46C, TP53, and DIS3 (particularly in nonhyperdiploid MM). Mutations were often present in subclonal populations, and multiple mutations within the same pathway (e.g., KRAS, NRAS, and BRAF) were observed in the same patient. In vitro modeling predicts only partial treatment efficacy of targeting subclonal mutations, and even growth promotion of nonmutated subclones in some cases. These results emphasize the importance of heterogeneity analysis for treatment decisions.
Year of Publication2014
JournalCancer cell
Volume25
Issue1
Pages91-101
Date Published (YYYY/MM/DD)2014/01/13
ISSN Number1535-6108
DOI10.1016/j.ccr.2013.12.015
PubMedhttp://www.ncbi.nlm.nih.gov/pubmed/24434212?dopt=Abstract