Comprehensive molecular profiling of 718 Multiple Myelomas reveals significant differences in mutation frequencies between African and European descent cases

Zarko Manojlovic, Austin Christofferson, Winnie S. Liang, Jessica Aldrich, Megan Washington, Shukmei Wong, Daniel Rohrer, Scott Jewell, Rick A. Kittles, Mary Derome, Daniel Auclair, David Wesley Craig, Jonathan Keats, John D. Carpten

Research output: Contribution to journalArticle

20 Scopus citations

Abstract

Multiple Myeloma (MM) is a plasma cell malignancy with significantly greater incidence and mortality rates among African Americans (AA) compared to Caucasians (CA). The overall goal of this study is to elucidate differences in molecular alterations in MM as a function of self-reported race and genetic ancestry. Our study utilized somatic whole exome, RNA-sequencing, and correlated clinical data from 718 MM patients from the Multiple Myeloma Research Foundation CoMMpass study Interim Analysis 9. Somatic mutational analyses based upon self-reported race corrected for ancestry revealed significant differences in mutation frequency between groups. Of interest, BCL7A, BRWD3, and AUTS2 demonstrate significantly higher mutation frequencies among AA cases. These genes are all involved in translocations in B-cell malignancies. Moreover, we detected a significant difference in mutation frequency of TP53 and IRF4 with frequencies higher among CA cases. Our study provides rationale for interrogating diverse tumor cohorts to best understand tumor genomics across populations.

Original languageEnglish (US)
Article numbere1007087
JournalPLoS genetics
Volume13
Issue number11
DOIs
StatePublished - Nov 2017

ASJC Scopus subject areas

  • Ecology, Evolution, Behavior and Systematics
  • Molecular Biology
  • Genetics
  • Genetics(clinical)
  • Cancer Research

Fingerprint Dive into the research topics of 'Comprehensive molecular profiling of 718 Multiple Myelomas reveals significant differences in mutation frequencies between African and European descent cases'. Together they form a unique fingerprint.

  • Cite this

    Manojlovic, Z., Christofferson, A., Liang, W. S., Aldrich, J., Washington, M., Wong, S., Rohrer, D., Jewell, S., Kittles, R. A., Derome, M., Auclair, D., Craig, D. W., Keats, J., & Carpten, J. D. (2017). Comprehensive molecular profiling of 718 Multiple Myelomas reveals significant differences in mutation frequencies between African and European descent cases. PLoS genetics, 13(11), [e1007087]. https://doi.org/10.1371/journal.pgen.1007087