Germline Testing Identifies Pathogenic/Likely Pathogenic Variants in Patients with Pancreatic Neuroendocrine Tumors.

Autor:	Mohindroo C; Department of Oncology, Johns Hopkins University School of Medicine, Baltimore, Maryland.; Department of Clinical Cancer Prevention, The University of Texas MD Anderson Cancer Center, Houston, Texas., Baydogan S; Department of Clinical Cancer Prevention, The University of Texas MD Anderson Cancer Center, Houston, Texas., Agarwal P; Department of Oncology, Abramson Cancer Center at the University of Pennsylvania, Philadelphia, Pennsylvania., Wright RD; Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas.; Clinical Cancer Genetics Program, The University of Texas MD Anderson Cancer Center, Houston, Texas., Prakash LR; Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas., Mork ME; Clinical Cancer Genetics Program, The University of Texas MD Anderson Cancer Center, Houston, Texas., Klein AP; Department of Oncology, Johns Hopkins University School of Medicine, Baltimore, Maryland., Laheru DA; Department of Oncology, Johns Hopkins University School of Medicine, Baltimore, Maryland., Maxwell JE; Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas., Katz MHG; Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas., Dasari A; Department of Gastrointestinal Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas., Kim MP; Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas., He J; Department of Surgical Oncology, Johns Hopkins University School of Medicine, Baltimore, Maryland., McAllister F; Department of Clinical Cancer Prevention, The University of Texas MD Anderson Cancer Center, Houston, Texas.; Clinical Cancer Genetics Program, The University of Texas MD Anderson Cancer Center, Houston, Texas.; Department of Gastrointestinal Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas.; Department of Immunology, The University of Texas MD Anderson Cancer Center, Houston, Texas., De Jesus-Acosta A; Department of Oncology, Johns Hopkins University School of Medicine, Baltimore, Maryland.
Jazyk:	angličtina
Zdroj:	Cancer prevention research (Philadelphia, Pa.) [Cancer Prev Res (Phila)] 2024 Jul 02; Vol. 17 (7), pp. 335-342.
DOI:	10.1158/1940-6207.CAPR-23-0483
Abstrakt:	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. (©2024 American Association for Cancer Research.)
Databáze:	MEDLINE
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