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

doi:10.1371/journal.pgen.1007087

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

PLoS Genet. 2017 Nov 22;13(11):e1007087. doi: 10.1371/journal.pgen.1007087. eCollection 2017 Nov.

Authors

Affiliations

¹ Department of Translational Genomics, Keck School of Medicine, University of Southern California, Los Angeles, CA, United States of America.
² Translational Genomics Research Institute, Phoenix, AZ, United States of America.
³ Van Andel Research Institute, Grand Rapids, MI, United States of America.
⁴ Department of Surgery, Division of Population Genetics, University of Arizona, Tuscon, AZ, United States of America.
⁵ Multiple Myeloma Research Foundation, Norwalk, CT, United States of America.

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.

MeSH terms

Adult
Black People / genetics
Cytoskeletal Proteins
Exome / genetics
Female
Genotype
High-Throughput Nucleotide Sequencing
Humans
Interferon Regulatory Factors / genetics*
Male
Microfilament Proteins / genetics*
Middle Aged
Multiple Myeloma / epidemiology
Multiple Myeloma / genetics*
Multiple Myeloma / pathology
Mutation
Mutation Rate
Oncogene Proteins / genetics*
Proteins / genetics*
Racial Groups
Transcription Factors / genetics*
Tumor Suppressor Protein p53 / genetics*
White People / genetics

Substances

AUTS2 protein, human
BCL7A protein, human
BRWD3 protein, human
Cytoskeletal Proteins
Interferon Regulatory Factors
Microfilament Proteins
Oncogene Proteins
Proteins
TP53 protein, human
Transcription Factors
Tumor Suppressor Protein p53
interferon regulatory factor-4

Grants and funding

This work was supported from Multiple Myeloma Research Foundation (CoMMpass) MMRF-TGen Carpten and USC-Carpten and Start-up Fund, University of Southern California to JDC. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.