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Sandy Srinivas, MD
Sandy Srinivas, MD
Posted: Tuesday, June 20, 2023
Using methylation profiling, researchers have identified specific somatic copy number alterations that seem to be linked to genetic ancestry and outcomes in primary prostate cancer. In JCI Insight, Tamara L. Lotan, MD, of Johns Hopkins University School of Medicine, Baltimore, and colleagues noted that chromosome 8q gains (including MYC) were significantly associated with biochemical recurrence and metastasis, independent of genetic ancestry. Also, the density of regulatory T cells in both Black and White patients appeared to be significantly correlated with the percent genome altered.
Few prior studies had examined the genome-wide copy number landscape and immune content of matched cohorts with genetic ancestry data and clinical outcomes. “We assessed [them in] a grade-matched, surgically treated cohort of 145 self-identified Black and 145 self-identified White patients with genetic ancestry estimation,” the team explained. Their models were adjusted for age, preoperative prostate-specific antigen levels, and Gleason Grade Group and were filtered for germline copy number variations.
Dr. Lotan and co-investigators identified 143 loci where copy number varied significantly by percent African ancestry, clustering on chromosomes 6p, 10q, 11p, 12p, and 17p. Genetic copy number variations may be confounders in somatic copy number alteration analyses, according to the authors, and may account for differences in immune gene expression reported by others regarding prostate tumors in Black versus White patients.
In fact, the region around PTEN showed relative increased copy number in patients with higher African ancestry, and similar findings emerged for a region on 17p near TP53, consistent with reports of less-frequent TP53 alterations in prostate tumors in self-identified Black patients. Several heretofore-unidentified regions with copy number variations by ancestry included clusters on 11p13, 6p24.1, and 12p12.1. The 8q region, including MYC—which was most closely associated with risk of metastatic disease in their cohorts—did not exhibit significant copy number variation by genetic ancestry in their analyses, despite prior reports suggesting more frequent amplification in Black men.
Disclosure: The study authors’ disclosure information can be found at insight.jci.org.
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