A novel genomic alteration of LSAMP associates with aggressive prostate cancer in African American men

Evaluation of cancer genomes in global context is of great interest in light of changing ethnic distribution of the world population. We focused our study on men of African ancestry because of their disproportionately higher rate of prostate cancer (CaP) incidence and mortality. We present a systematic whole genome analyses, revealing alterations that differentiate African American (AA) and Caucasian American (CA) CaP genomes. We discovered a recurrent deletion on chromosome 3q13.31 centering on the LSAMP locus that was prevalent in tumors from AA men (cumulative analyses of 435 patients: whole genome sequence, 14; FISH evaluations, 101; and SNP array, 320 patients). Notably, carriers of this deletion experienced more rapid disease progression. In contrast, PTEN and ERG common driver alterations in CaP were significantly lower in AA prostate tumors compared to prostate tumors from CA. Moreover, the frequency of inter-chromosomal rearrangements was significantly higher in AA than CA tumors. These findings reveal differentially distributed somatic mutations in CaP across ancestral groups, which have implications for precision medicine strategies. •Distinct genomic alterations were defined in prostate cancers of African American (AA) and Caucasian American (CA) men.•A novel prevalent deletion of the LSAMP locus associated with prostate cancer recurrence in AA prostate cancers•Focused evaluations of cancer genomes in the context of ethnicity have implications in enhancing precision medicine. Men of African ancestry experience a disproportionately higher rate of prostate cancer (CaP) incidence and mortality. However, most prostate cancer genome evaluations thus far have focused on men of European ancestry. This report highlights a new recurrent genomic alteration of LSAMP locus in African American prostate cancers. Further, significant differences of two established prostate cancer driver genes, ERG and PTEN, were affirmed. This study conveys the need for careful evaluations of cancer genomes in global context with important implications for precision medicine strategies.