AI Article Synopsis
- Thousands of somatic single-nucleotide variants (SNVs) found in tumors have unknown functions, but studies show they are more common in prostate tumors than in adjacent normal tissue, particularly around key transcription regulators like AR, FOXA1, and HOXB13.
- These SNVs are often located in the same regions as genetic predispositions linked to prostate cancer, especially at the 8q24 locus, which affects MYC gene expression.
- Despite this accumulation of SNVs in important areas of the genome, experiments indicate that very few of these variants actually change how well cis-regulatory elements can activate genes crucial for prostate cancer development.
Article Abstract
Thousands of noncoding somatic single-nucleotide variants (SNVs) of unknown function are reported in tumors. Partitioning the genome according to cistromes reveals the enrichment of somatic SNVs in prostate tumors as opposed to adjacent normal tissue cistromes of master transcription regulators, including AR, FOXA1, and HOXB13. This parallels enrichment of prostate cancer genetic predispositions over these transcription regulators' tumor cistromes, exemplified at the 8q24 locus harboring both risk variants and somatic SNVs in cis-regulatory elements upregulating MYC expression. However, Massively Parallel Reporter Assays reveal that few SNVs can alter the transactivation potential of individual cis-regulatory elements. Instead, similar to inherited risk variants, SNVs accumulate in cistromes of master transcription regulators required for prostate cancer development.
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| http://dx.doi.org/10.1016/j.ccell.2019.10.005 | DOI Listing |
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