Genomic and Immune Landscape of Pancreatic Ductal Adenocarcinoma Associated with Germline Pathogenic Variants in ATM.

ABSTRACT:

Purpose

Germline pathogenic variants (PV) in ATM increase the risk of pancreatic ductal adenocarcinoma (PDAC), but the underlying tumor biology of PDAC associated with germline PV in ATM has not been adequately explored.

Experimental design

Whole-genome, whole-exome, and RNA sequencing were performed on PDAC tumors from 25 germline ATM PV carriers diagnosed at Mayo Clinic between 2007 and 2017. Somatic and copy-number alterations, mutational signatures, transcriptomic subtypes, and the immune landscape were evaluated.

Results

High-quality whole-exome and whole-genome sequencing were obtained from 21 and 15 tumors, respectively. Biallelic inactivation of ATM was observed in 87%, KRAS PV in 90%, CDKN2A homozygous loss in 60%, and TP53 alterations in <10% of these tumors

SUBMITTER: Yadav S 

PROVIDER: S-EPMC12500237 | biostudies-literature | 2025 Nov

REPOSITORIES: biostudies-literature