Researchers have identified clinically relevant mutations that may be used to better stratify patients with myeloma at presentation, according to a study published online ahead of print in the Journal of Clinical Oncology.

Whole genome sequencing was performed on 463 patients who were enrolled onto the National Cancer Research Institute Myeloma XI trial, for whom complete molecular cytogenetic and clinical outcomes data were available.

Findings revealed 15 significantly mutated genes. The mutational spectrum is dominated by mutations in the RAS (43%) and nuclear factor-kB (17%) pathways. Although they are prognostically neutral, they could be exploited as therapeutic targets.

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Mutations in CCND1 and DNA repair pathway alterations (TP53, ATM, ATR, and ZNFHX4 mutations) are linked to a negative impact on survival. However, those in IRF4 and EGR1 are linked with a favorable overall survival.

These novel mutation risk factors were combined with the recurrent molecular adverse features and international staging system to generate an international staging system mutation score that can identify a high-risk population of patients who experience relapse and die prematurely.


  1. Walker BA, Boyle EM, Wardell CP, et al. Mutational spectrum, copy number changes, and outcome: results of a sequencing study of patients with newly diagnosed melanoma. J Clin Oncol. 2015. [epub ahead of print]. doi: 10.1200/JCO.2014.59.1503.