Pathogenic ATM Mutations in Cancer and a Genetic Basis for Radiotherapeutic Efficacy.

ABSTRACT:

Background

Radiation therapy is one of the most commonly used cancer therapeutics but genetic determinants of clinical benefit are poorly characterized. Pathogenic germline variants in ATM are known to cause ataxia-telangiectasia, a rare hereditary syndrome notable for marked radiosensitivity. In contrast, somatic inactivation of ATM is a common event in a wide variety of cancers, but its clinical actionability remains obscure.

Methods

We analyzed 20 107 consecutively treated advanced cancer patients who underwent targeted genomic sequencing as part of an institutional genomic profiling initiative and identified 1085 harboring a somatic or germline ATM mutation, including 357 who received radiotherapy (RT). Outcomes of irradiated tumors harboring ATM loss-of-function (LoF) m

SUBMITTER: Pitter KL 

PROVIDER: S-EPMC7936050 | biostudies-literature | 2021 Mar

REPOSITORIES: biostudies-literature