Targeting Germline- and Tumor-Associated Nucleotide Excision Repair Defects in Cancer.

ABSTRACT:

Purpose

Nucleotide excision repair (NER) gene alterations constitute potential cancer therapeutic targets. We explored the prevalence of NER gene alterations across cancers and putative therapeutic strategies targeting these vulnerabilities.

Experimental design

We interrogated our institutional dataset with mutational data from more than 40,000 patients with cancer to assess the frequency of putative deleterious alterations in four key NER genes. Gene-edited isogenic pairs of wild-type and mutant ERCC2 or ERCC3 cell lines were created and used to assess response to several candidate drugs.

Results

We found that putative damaging germline and somatic alterations in NER genes were present with frequencies up to 10% across multiple cancer types. Both in

SUBMITTER: Topka S 

PROVIDER: S-EPMC8191507 | biostudies-literature | 2021 Apr

REPOSITORIES: biostudies-literature