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The varied distribution and impact of RAS codon and other key DNA alterations across the translocation cyclin D subgroups in multiple myeloma

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.

Publication metadata

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


DOI: 10.18632/oncotarget.15718


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Funder referenceFunder name
P01 CA 55819