Candidate variants in DNA replication and repair genes in early-onset renal cell carcinoma patients referred for germline testing.

ABSTRACT:

Background

Early-onset renal cell carcinoma (eoRCC) is typically associated with pathogenic germline variants (PGVs) in RCC familial syndrome genes. However, most eoRCC patients lack PGVs in familial RCC genes and their genetic risk remains undefined.

Methods

Here, we analyzed biospecimens from 22 eoRCC patients that were seen at our institution for genetic counseling and tested negative for PGVs in RCC familial syndrome genes.

Results

Analysis of whole-exome sequencing (WES) data found enrichment of candidate pathogenic germline variants in DNA repair and replication genes, including multiple DNA polymerases. Induction of DNA damage in peripheral blood monocytes (PBMCs) significantly elevated numbers of [Formula: see text]H2AX foci, a marker of double-stranded breaks

SUBMITTER: Demidova EV 

PROVIDER: S-EPMC10123997 | biostudies-literature | 2023 Apr

REPOSITORIES: biostudies-literature