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

Abstract

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.

Genome-Wide Association Study Identifies African-Specific Susceptibility Loci in African Americans With Inflammatory Bowel Disease

“…Its protein product is also expressed in colon and platelets. Interestingly, LSAMP somatic deletions were associated with prostate cancer specifically in AAs 25 . The top ranked variant, rs72947885, is located in the 3’UTR and also overlaps with several transcriptional regulator motifs and is also reported by Ensembl to be in an enhancer region (ENSR00001988698) in some cell lines including B cells and M1 macrophages from venous blood.…”

Integrated Analysis of Genetic Ancestry and Genomic Alterations across Cancers

“…This shared genetic background may confer similarities in cancer incidence and outcomes in populations. Recent large-scale genomic profile studies in individual cancer types, such as prostate (Huang et al, 2017; Petrovics et al, 2015; Powell et al, 2013; Wang et al, 2017), breast (Ademuyiwa et al, 2017; Huo et al, 2017; Keenan et al, 2015; Loo et al, 2011), colon (Guda et al, 2015), lung (Araujo et al, 2015; Campbell et al, 2017; Kytola et al, 2017), gastric (Schumacher et al, 2017), esophageal (Deng et al, 2017), and kidney (Krishnan et al, 2016) cancers have robustly demonstrated that genomic differences in cancers exist among distinct racial and ethnic populations. Consistently, it has been reported that the genetic background of patients may influence specific somatic alterations in cancer genomes during tumorigenesis (Carter et al, 2017).…”

Self-declared ethnicity and genomic ancestry in prostate cancer patients from Brazil

“…Previous studies using AIMs have revealed the susceptibility of PCa association analyses to such confounding influence, and the need to take into account substructure caused by differences in relative ancestral genetic contributions between cases and controls (Erdei et al, 2011;Ricks-Santi et al, 2012;Petrovics et al, 2015). Prior investigations have explored the relationship between "skin color" and genomic ancestry estimated by AIMs Reddy et al, 2003;Pimenta et al, 2006;Suarez-Kurtz et al, 2007;Whitman et al, 2010;Lins et al, 2011;Ricks-Santi et al, 2012).…”