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.
Highlights
Multiple Myeloma (MM) is a malignancy of plasma cells provoked by immunoglobulin gene rearrangements, accounting for slightly more than 10% of all hematologic cancer diagnoses in the US [1,2,3]
We revealed significant differences in mutation frequencies for important cancer genes between AA and CA MM
African American (AA) patients matched for socioeconomics, age, and gender are three times more likely to be diagnosed with MM, and with death rates that double those observed among Caucasians (CA) [4, 8, 9]
Summary
Multiple Myeloma (MM) is a malignancy of plasma cells provoked by immunoglobulin gene rearrangements, accounting for slightly more than 10% of all hematologic cancer diagnoses in the US [1,2,3]. Pathogenesis evolves from an asymptomatic premalignant stage of clonal plasma cell proliferation termed “monoclonal gammopathy of undetermined significance” (MGUS) [4, 5]. MGUS is present in more than 3% of the population above the age of 50 and progresses to MM, or related malignancy at a rate of 1% per year [2, 6]. African American (AA) patients matched for socioeconomics, age, and gender are three times more likely to be diagnosed with MM, and with death rates that double those observed among Caucasians (CA) [4, 8, 9]. A deeper understanding of oncogenic processes driving MM pathogenesis in statistically powered multi-ethnic cohorts is still needed to addressing disparities in incidence and outcomes observed among AA or otherwise African descent patients
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