Uncovering the biology of multiple myeloma among African Americans: a comprehensive genomics approach

Abstract

Epidemiological data have suggested that African American (AA) persons are twice as likely to be diagnosed with multiple myeloma (MM) compared with European American (EA) persons. Here, we have analyzed a set of cytogenetic and genomic data derived from AA and EA MM patients. We have compared the frequency of IgH translocations in a series of data from 115 AA patients from 3 studies and 353 EA patients from the Eastern Cooperative Oncology Group (ECOG) studies E4A03 and E9487. We have also interrogated tumors from 45 AA and 196 EA MM patients for somatic copy number abnormalities associated with poor outcome. In addition, 35 AA and 178 EA patients were investigated for a transcriptional profile associated with high-risk disease. Overall, based on this cohort, genetic profiles were similar except for a significantly lower frequency of IgH translocations (40% vs 52%; P = .032) in AA patients. Frequency differences of somatic copy number aberrations were not significant after correction for multiple testing. There was also no significant difference in the frequency of high-risk disease based on gene expression profiling. Our study represents the first comprehensive comparisons of the frequency and distribution of molecular alterations in MM tumors between AA and EA patients. ECOG E4A03 is registered with ClinicalTrials.gov, number NCT00098475. ECOG E9487 is a companion validation set to the ECOG study E9486 and is registered with the National Institutes of Health, National Cancer Institute, Clinical Trials (PDQ), number EST-9486.

Figures

Figure 1

Classification of AA and EA patients by MM subtype using aCGH. Penetrance plots are shown depicting chromosome gains (red) and losses (green) from the analysis of tumor DNA from MM patients. Data were visualized using DNA Analytics software (Agilent). Patients were grouped by race and stratified into the 2 major subtypes, H-MM and NH-MM. Subtype frequencies were compared between the 2 groups: (A) AA H-MM (53%), (B) AA NH-MM (47%), (C) EA H-MM (53%), and (D) EA NH-MM (47%).