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August 19, 2025Clinical Cancer Research

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

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Authors

SYSiddhartha YadavRBRiyue BaoRGRondell P. Graham

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Overview

Analysis reveals unique mutational signatures and immune characteristics in pancreatic ductal adenocarcinoma with germline ATM variants, suggesting targeted therapies may be beneficial.

Key Points

  • Biallelic inactivation of ATM was found in 87% of tumors, indicating a significant impact of these germline variants on tumor biology.
  • A predominant clock-like mutational signature appeared across all samples, highlighting a unique genomic feature of these pancreatic ductal adenocarcinomas.
  • Whole-genome and RNA-sequencing were employed to characterize tumors from 25 germline ATM variant carriers, providing insights into their development.
  • Differences in immune landscape and mutational profiles suggest potential targeted therapeutic strategies for patients with germline ATM variants.

Cite This Study

Yadav et al. (2025) studied this question.

synapsesocial.com/papers/68af35e3cf1dd9ea359e9efdhttps://doi.org/10.1158/1078-0432.ccr-24-4120
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Also Consider

Synapse has enriched 5 closely related papers on similar clinical questions. Consider them for comparative context:

  1. 1Prevalence and impact of germline mutations in pancreatic ductal adenocarcinoma2026
  2. 2Exploiting TGF-β-mediated Stromal Programming in Homologous Recombination-Deficient Pancreatic Cancer2025
  3. 3Integrative Multiomic and Deep Learning Profiling of KRAS Mutant and Wildtype Genomes in Pancreatic Tumorigenesis2025
  4. 4Germline Genetic Profiling Utilizing Multigene Panel Testing in Jordanian Patients with Pancreatic Cancer. A Comprehensive Cancer Center Experience2025
  5. 5Drivers of Pancreatic Cancer: Beyond the Big 42025