Widespread genetic heterogeneity in multiple myeloma: implications for targeted therapy
By Jens G. Lohr, P. Stojanov, Scott L. Carter, Peter Cruz-Gordillo, M. Lawrence, D. Auclair, C. Sougnez, B. Knoechel, Joshua Gould, G. Saksena and 11 more. Cancer Cell, 2014
944 citations recorded by the source corpus.
SUMMARY We 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 non-hyperdiploid 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 non-mutated subclones in some cases. These results emphasize the importance of heterogeneity analysis for treatment decisions.
Subfields: Cancer Research, Hematology, Molecular Biology
View Paper: https://www.semanticscholar.org/paper/230bd411c3cd38d5a7564cb055883589408afaf6
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Citations in the corpus
- Biological and therapeutic impact of intratumor heterogeneity in cancer evolution. (2015, background): “…myeloma (MM), driver events such asBRAFmutations can be clonal in some patients and subclonal in others, where they can co-occur with RAS mutations, suggesting these alterations can contribute to either tumor initiation or maintenance and progression (Bolli et al., 2014; Lohr et al., 2014).”
- Vemurafenib in Multiple Nonmelanoma Cancers with BRAF V600 Mutations (2015, neutral): “(%) 8 (42) 0 1 (4) 1 (12) 5 (36) 1 (14)”
- Genomic characterization of brain metastases reveals branched evolution and potential therapeutic targets (2015, neutral): “their cancer-cell fraction (or CCF) (16, 18-21).”