Pathogenic Germline Mutational Landscape in Patients With Renal Cell Carcinoma and Associated Clinicopathologic Features.

Autor:	Nguyen CB; Rogel Comprehensive Cancer Center, University of Michigan, Ann Arbor, MI., Knaus C; Department of Internal Medicine, University of Michigan, Ann Arbor, MI., Li J; Department of Biostatistics, School of Public Health, University of Michigan, Ann Arbor, MI., Accardo ML; Department of Internal Medicine, University of Michigan, Ann Arbor, MI., Koeppe E; Department of Internal Medicine, University of Michigan, Ann Arbor, MI., Vaishampayan UN; Rogel Comprehensive Cancer Center, University of Michigan, Ann Arbor, MI., Alva AS; Rogel Comprehensive Cancer Center, University of Michigan, Ann Arbor, MI., Else T; Rogel Comprehensive Cancer Center, University of Michigan, Ann Arbor, MI.; Division of Metabolism, Endocrinology, and Diabetes, Department of Internal Medicine, University of Michigan, Ann Arbor, MI.
Jazyk:	angličtina
Zdroj:	JCO precision oncology [JCO Precis Oncol] 2023 Sep; Vol. 7, pp. e2300168.
DOI:	10.1200/PO.23.00168
Abstrakt:	Purpose: A subset of renal cell carcinoma (RCC) cases occur because of a hereditary predisposition. However, the prevalence and profiling of germline alterations in RCC have not been fully characterized. Additionally, clinicopathologic factors associated with pathogenic or likely pathogenic (P/LP) germline variants in patients with RCC remain poorly understood. Methods: A retrospective analysis of patients with RCC who underwent genetic evaluation was performed. The frequency of P/LP germline variants and genes was evaluated in this cohort. The association between genetic testing outcomes and clinicopathologic features was also assessed. Results: A total of 321 patients with RCC who had germline testing were identified. Within this cohort, 42 patients (13.1%) had P/LP variants. Genes with the most frequent germline mutations were FLCN (n = 10, 3.1%), SDHB (n = 4, 1.2%), VHL (n = 4, 1.2%), MLH1 (n = 3, 0.9%), and CHEK2 (n = 4, 1.2%). Among patients with P/LP variants, 19 (45.2%) had a potentially targetable mutation. The presence of bilateral or multifocal tumors was associated with P/LP variants ( P = .0012 and P = .0098, respectively). Patients who had targeted gene testing had higher rates of P/LP variants compared with multigene panel testing ( P = .015). Age and family history of cancers (RCC and non-RCC) did not have any statistically significant association with germline testing outcomes. Conclusion: Among patients with RCC, unselected for a known familial predisposition, 13.4% had P/LP variants. Almost half of patients with P/LP variants had a potentially targetable mutation. Targeted gene panel testing is a feasible option for patients, particularly if syndromic features are present. Age and family history were not associated with P/LP variants. Future studies are needed to optimize current genetic evaluation criteria to expand the detection of patients with RCC who may have germline mutations.
Databáze:	MEDLINE
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