Genomic and Clinicopathologic Characterization of ATM-deficient Prostate Cancer.

Clinical Cancer Research : an Official Journal of the American Association for Cancer Research
Harsimar KaurTamara L Lotan

Abstract

The ATM (ataxia telangiectasia mutated) gene is mutated in a subset of prostate cancers, and ATM mutation may confer specific therapeutic vulnerabilities, although ATM-deficient prostate cancers have not been well-characterized. We genetically validated a clinical grade IHC assay to detect ATM protein loss and examined the frequency of ATM loss among tumors with pathogenic germline ATM mutations and genetically unselected primary prostate carcinomas using tissue microarrays (TMAs). Immunostaining results were correlated with targeted somatic genomic sequencing and clinical outcomes. ATM protein loss was found in 13% (7/52) of primary Gleason pattern 5 cancers with available sequencing data and was 100% sensitive for biallelic ATM inactivation. In a separate cohort with pathogenic germline ATM mutations, 74% (14/19) had ATM protein loss of which 70% (7/10) of evaluable cases had genomic evidence of biallelic inactivation, compared with zero of four of cases with intact ATM expression. By TMA screening, ATM loss was identified in 3% (25/831) of evaluable primary tumors, more commonly in grade group 5 (17/181; 9%) compared with all other grades (8/650; 1%; P < 0.0001). Of those with available sequencing, 80% (4/5) with homogeneous...Continue Reading

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Citations

Jan 20, 2021·Modern Pathology : an Official Journal of the United States and Canadian Academy of Pathology, Inc·Tamara L LotanEmmanuel S Antonarakis
Jan 23, 2021·Cells·Vincenza ConteducaPasquale Rescigno
Jul 3, 2021·The Urologic Clinics of North America·Matthew J Schiewer, Karen E Knudsen

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