The Evolving Paradigm of Germline Testing in Pancreatic Ductal Adenocarcinoma and Implications for Clinical Practice

Chirayu Mohindroo; Ana De Jesus-Acosta; Matthew B Yurgelun; Anirban Maitra; Maureen Mork; Florencia McAllister

doi:10.1016/j.path.2022.05.004

The Evolving Paradigm of Germline Testing in Pancreatic Ductal Adenocarcinoma and Implications for Clinical Practice

Surg Pathol Clin. 2022 Sep;15(3):491-502. doi: 10.1016/j.path.2022.05.004. Epub 2022 Aug 2.

Authors

Chirayu Mohindroo¹, Ana De Jesus-Acosta², Matthew B Yurgelun³, Anirban Maitra⁴, Maureen Mork⁵, Florencia McAllister⁶

Affiliations

¹ Department of Clinical Cancer Prevention, The University of Texas MD Anderson Cancer Center, 1515 Holcombe, Unit 1360, Houston, TX 77030, USA; Department of Internal Medicine, Sinai Hospital of Baltimore, 2435 W. Belvedere Ave, Ste 56, Baltimore, MD 21215, USA.
² Department of Oncology, The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Johns Hopkins University School of Medicine, 401 North Broadway, Baltimore, MD 21231, USA.
³ Department of Medical Oncology, Dana-Farber Cancer Institute, 450 Brookline Avenue, Boston, MA 02215, USA.
⁴ Department of Translational Molecular Pathology, Sheikh Ahmed Center for Pancreatic Cancer Research, The University of Texas MD Anderson Cancer Center, 2130 West Holcombe Boulevard, Houston, TX 77030, USA.
⁵ Clinical Cancer Genetics Program, The University of Texas MD Anderson Cancer Center, 1515 Holcombe, Houston, TX 77030, USA.
⁶ Department of Clinical Cancer Prevention, The University of Texas MD Anderson Cancer Center, 1515 Holcombe, Unit 1360, Houston, TX 77030, USA; Clinical Cancer Genetics Program, The University of Texas MD Anderson Cancer Center, 1515 Holcombe, Houston, TX 77030, USA; Department of Gastrointestinal Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA; Department of Immunology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA. Electronic address: FMcallister@mdanderson.org.

PMID: 36049831
DOI: 10.1016/j.path.2022.05.004

Abstract

Identification of deleterious germline mutations in pancreatic ductal adenocarcinoma (PDAC) patients can have therapeutic implications for the patients and result in cascade testing and prevention in their relatives. Universal testing for germline mutations is now considered standard of care in patients with PDAC, regardless of family history, personal history, or age. Here, we highlight the commonly identified germline mutations in PDAC patients as well as the impact of multigene panel testing. We further discuss therapeutic implications of germline testing on the index cases, and the impact of cascade testing on cancer early detection and prevention in relatives.

Keywords: Cancer screening; Genetic testing; Germline mutations; Immunotherapy; Multigene panel testing; PARP inhibitors; Pancreatic ductal adenocarcinoma.

Publication types

Review

MeSH terms

Carcinoma, Pancreatic Ductal* / diagnosis
Carcinoma, Pancreatic Ductal* / genetics
Genetic Predisposition to Disease
Genetic Testing
Germ Cells / pathology
Germ-Line Mutation / genetics
Humans
Pancreatic Neoplasms* / diagnosis
Pancreatic Neoplasms* / genetics
Pancreatic Neoplasms* / pathology