Assessing Determinants of Response to PARP Inhibition in Germline <i>ATM</i> Mutant Melanoma.

ABSTRACT: The ataxia-telangiectasia-mutated (ATM) protein plays a crucial role in the DNA damage response, particularly in the homologous recombination (HR) pathway. This study aimed to assess the impact of deleterious ATM variants on homologous recombination deficiency (HRD) and response to PARP inhibitors (PARPi) in melanoma patients, using a cell line established from melanoma tissue of a patient carrying the c.5979_5983del germline ATM variant. Despite proven loss of heterozygosity, lack of ATM activation, and HRD, our model did not show sensitivity to PARPi. We assessed the potential contribution of the Schlafen family member 11 (SLFN11) helicase, whose expression is inversely correlated with PARPi sensitivity in other cancers, to the observed resistance. The ATM mutant cell line

SUBMITTER: Allavena E 

PROVIDER: S-EPMC12346925 | biostudies-literature | 2025 Aug

REPOSITORIES: biostudies-literature