ERCC4
Overview
ERCC4 (Excision Repair Cross-Complementation Group 4), also known as XPF, encodes the nuclease subunit of the ERCC1-XPF endonuclease complex, which is essential for the 5’ incision step in nucleotide excision repair (NER). Loss-of-function mutations in ERCC4 impair NER, leading to accumulation of DNA lesions and elevated mutational burden. In cancer genomics, ERCC4 is identified as a DNA damage repair (DDR) gene whose somatic alteration contributes to mutational burden and potential immunotherapy sensitivity, particularly in bladder cancer.
Alterations observed in the corpus
- Less frequent DDR alteration in high-grade NMIBC, contributing to the 30% DDR-altered fraction of high-grade disease PMID:28583311
Cancer types (linked)
- BLCA — identified as a DDR gene altered in high-grade non-muscle-invasive bladder cancer (NMIBC); DDR-altered tumors carry markedly elevated mutational burden, supporting checkpoint immunotherapy PMID:28583311
Co-occurrence and mutual exclusivity
Therapeutic relevance
- Elevated mutational burden in DDR-altered (including ERCC4-mutant) high-grade NMIBC supports trials of PD-1/PD-L1 checkpoint inhibitors such as atezolizumab PMID:28583311
Open questions
- The clinical significance of individual ERCC4 mutations vs. the broader DDR-altered class in predicting immunotherapy response in NMIBC requires prospective validation.
Sources
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