Journal article
Germline Testing Identifies Pathogenic/Likely Pathogenic Variants in Patients with Pancreatic Neuroendocrine Tumors
Cancer prevention research (Philadelphia, Pa.), Vol.17(7), pp.335-342
07/02/2024
DOI: 10.1158/1940-6207.CAPR-23-0483
PMID: 38662083
Abstract
Ten percent of pancreatic neuroendocrine tumors (pNET) are related to inherited syndromes (MEN1, MEN4, VHL, NF1, and TSC). Growing evidence suggests that clinically sporadic pNETs can also harbor germline pathogenic variants. In this study, we report the prevalence of pathologic/likely pathologic (P/LP) germline variants in a high-risk cohort and an unselected cohort. We collected clinical data of patients with pNETs seen at MD Anderson Cancer Center and Johns Hopkins Hospital. The high-risk cohort included (n = 132) patients seen at MD Anderson Cancer Center who underwent germline testing for high-risk criteria (early onset, personal or family history of cancer, and syndromic features) between 2013 and 2019. The unselected cohort included (n = 106) patients seen at Johns Hopkins Hospital who underwent germline testing following their diagnosis of pNETs between 2020 and 2022. In the high-risk cohort (n = 132), 33% (n = 44) had P/LP variants. The majority of the patients had P/LP variants in MEN1 56% (n = 25), followed by DNA repair pathways 18% (n = 8), and 7% (n = 3) in MSH2 (Lynch syndrome). Patients with P/LP were younger (45 vs. 50 years; P = 0.002). In the unselected cohort (n = 106), 21% (n = 22) had P/LP. The majority were noted in DNA repair pathways 40% (n = 9) and MEN1 36% (n = 8). Multifocal tumors correlated with the presence of P/LP (P = 0.0035). MEN1 germline P/LP variants correlated with younger age (40 vs. 56 years; P = 0.0012), presence of multifocal tumors (P < 0.0001), and World Health Organization grade 1 histology (P = 0.0078). P/LP variants are prevalent in patients with clinically sporadic pNET irrespective of high-risk features. The findings support upfront universal germline testing in all patients with pNET. Prevention Relevance: Here, we present germline data from the largest reported cohort of patients with pNET (n = 238), comprising both a high-risk cohort and an unselected cohort. In both cohorts, we identify a high number of P/LPs, including those in the DNA repair pathway. Our findings support universal germline testing in patients with pNET.
Details
- Title: Subtitle
- Germline Testing Identifies Pathogenic/Likely Pathogenic Variants in Patients with Pancreatic Neuroendocrine Tumors
- Creators
- Chirayu Mohindroo - The University of Texas MD Anderson Cancer CenterSeyda Baydogan - The University of Texas MD Anderson Cancer CenterParul Agarwal - University of PennsylvaniaRobin D. Wright - The University of Texas MD Anderson Cancer CenterLaura R. Prakash - The University of Texas MD Anderson Cancer CenterMaureen E. Mork - The University of Texas MD Anderson Cancer CenterAlison P. Klein - Johns Hopkins UniversityDaniel A. Laheru - Johns Hopkins UniversityJessica E. Maxwell - The University of Texas MD Anderson Cancer CenterMatthew H. G. Katz - The University of Texas MD Anderson Cancer CenterArvind Dasari - The University of Texas MD Anderson Cancer CenterMichael P. Kim - The University of Texas MD Anderson Cancer CenterJin He - Johns Hopkins UniversityFlorencia Mcallister - The University of Texas MD Anderson Cancer CenterAna De Jesus-Acosta - Johns Hopkins University
- Resource Type
- Journal article
- Publication Details
- Cancer prevention research (Philadelphia, Pa.), Vol.17(7), pp.335-342
- DOI
- 10.1158/1940-6207.CAPR-23-0483
- PMID
- 38662083
- ISSN
- 1940-6207
- eISSN
- 1940-6215
- Publisher
- Amer Assoc Cancer Research
- Number of pages
- 8
- Grant note
- V Foundation Shelby-Lavine Pancreatic Scholars Program RP200173 / Cancer Prevention Research Institute of Texas; Cancer Prevention & Research Institute of Texas Sabin Family Foundation 1R37CA237384 / NCI; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Cancer Institute (NCI)
- Language
- English
- Date published
- 07/02/2024
- Academic Unit
- Internal Medicine
- Record Identifier
- 9985178656502771
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