Paired BM MM cell DNA and ctDNA from 33 relapsed/refractory (RR) and 15 newly diagnosed (ND) patients were analysed for KRAS, NRAS, BRAF and TP53 mutations using the OnTarget Mutation Detection (OMD) platform.
KRAS and NRAS exon 3 mutations were significantly associated with the myeloma cohort compared with non-myeloma plasma cell dyscrasias (odds ratio (OR) 9.87, 95% confidence interval (CI) 1.07-90.72, P=0.043 and OR 7.03, 95% CI 1.49-33.26, P=0.014).
Multiple myeloma (MM) was characterized by frequent mutations in KRAS/NRAS/BRAF within the EGFR pathway that could induce resistance to EGFR inhibitors.
We used deep sequencing to screen 167 representative patients with PC dyscrasias [132 with MM, 24 with primary PC leukemia (pPCL) and 11 with secondary PC leukemia (sPCL)] for mutations in BRAF, NRAS and KRAS, which were respectively found in 12%, 23.9% and 29.3% of cases.
These findings identify a significant clinical impact of NRAS mutation in myeloma and demonstrate a clear example of functional differences between the KRAS and NRAS oncogenes.
We observed frequent mutations in KRAS (particularly in previously treated patients), NRAS, BRAF, FAM46C, TP53, and DIS3 (particularly in nonhyperdiploid MM).
Here, we report a mutation analysis of N- and K-Ras genes in purified plasma cell populations from a panel of 81 newly diagnosed MM patients stratified according to the most frequent genetic and molecular features associated with the neoplasia.
To address this issue in myeloma, we used the ANBL-6 myeloma cell line where interleukin (IL)-6-dependent cells are stably transfected with mutated N-ras or K-ras genes.