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Lookup NU author(s): Professor Graham Jackson
This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0).
We examined a set of 805 cases that underwent DNA sequencing using the FoundationOne Heme (F1H) targeted sequencing panel and gene expression profiling. Known and likely variant calls from the mutational data were analyzed for significant associations with gene expression defined translocation cyclin D (TC) molecular subgroups. The spectrum of KRAS, NRAS, and BRAF codon mutations varied across subgroups with NRAS mutations at Q61 codon being common in hyperdiploid (HRD) and t(11;14) myeloma while being rare in MMSET and MAF. In addition, the presence of RASRAF mutations was inversely associated with NFκB pathway activation in all subgroups excluding MAF. In the MMSET subgroup, cases with low FGFR3 expression frequently had RAS-RAF mutations. Conditional inference tree analysis determined that mutation and homozygous deletion of TP53, CDKN2C, and RB1 were key prognostic factors associated with adverse outcome in a non-relapse clinical setting. In conclusion, this study highlights the heterogeneity in the distribution and clinical outcomes of RAS codon and other mutations in multiple myeloma dependent upon primary molecular subgroup.
Author(s): Stein CK, Pawlyn C, Chavan S, Rasche L, Weinhold N, Corken A, Buros A, Sonneveld P, Jackson GH, Landgren O, Mughal T, He J, Barlogie B, Bergsagel PL, Davies FE, Walker BA, Morgan GJ
Publication type: Article
Publication status: Published
Journal: Oncotarget
Year: 2017
Volume: 8
Issue: 17
Pages: 27854-27867
Online publication date: 24/02/2017
Acceptance date: 15/02/2017
Date deposited: 24/05/2017
ISSN (print): 1949-2553
Publisher: Impact Journals LLC
URL: https://doi.org/10.18632/oncotarget.15718
DOI: 10.18632/oncotarget.15718
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