A study of of allele-specific chromatin activity in prostate tumors is now out in The American Journal of Human Genetics, led by the highly talented undergraduate researcher Anamay Shetty:

Allele-specific epigenetic activity in prostate cancer and normal prostate tissue implicates prostate cancer risk mechanisms.
Shetty A, Seo JH, Bell CA, O’Connor EP, Pomerantz M, Freedman ML [+], Gusev A [+]. The American Journal of Human Genetics. 2021

This study identified >7,000 active epigenetic features in tumors that harbored germline variants with allele-specific activity, indicative of a germline-somatic interaction influencing chromatin activity in the tumor. These allele-specific variants were linked to a broad range of transcription factors relevant to prostate cancer as well as extensive collaborative/co-operative binding across multiple transcription factor pairs. Intriguingly, allele-specific enhancer activity in the tumors (but not in the normals) was significantly enriched for prostate cancer GWAS risk variants. This work adds to the growing list of studies showing germline effects in the tumor can potentially illuminate the mechanisms of cancer risk, and in fact be more relevant than molecular observations from the normal cell.

All significant variants and full allele-specific outputs are publicly available here.

Figure: Enrichment of GWAS (left) and eQTLs (right) at allele-specific regulatory variants in prostate tissue states.

schematic