Association of ATM mutations in metastatic prostate cancer with differential genomic alteration profiles from homologous recombination deficient and proficient tumors

Authors:

Charles J. Ryan, Julie Elaine McGrath, Joanne Xiu, Justin Hwang, Chadi Nabhan, Andre Luiz De Souza, Pedro C. Barata, Shuchi Gulati, Shuanzeng Wei, Jaime R. Merchan, Arpit Rao, Daniel M. Geynisman, Inas Abuali, Wolfgang Michael Korn, Elisabeth I. Heath

Background: ATM mutations, one of a family of DNA repair defects prevalent in prostate cancer, have been included in a list of actionable mutations for PARP inhibitor (PARPi) therapeutic trials. Despite preclinical evidence, PARPi have shown minimal clinical activity in ATM mutant prostate cancer (ATMmPCa). The present analysis explores co-occurring genomic alterations that may drive outcomes of metastatic PCa (mPCa) patients with tumors harboring ATM mutations and provide clues for understanding therapy resistance and potential targets.

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