A Germline BRCA2 Pathogenic Variant Identified by Multigene Panel Testing in Upper Tract Urothelial Carcinoma

Abstract

ABSTRACT Introduction Upper tract urothelial carcinoma (UTUC) is associated with Lynch syndrome; however, increasing evidence suggests broader genetic heterogeneity. Although multigene panel testing (MGPT) is increasingly adopted internationally, syndrome‐specific genetic testing (SSGT) remains predominant in Japan, potentially limiting detection of non‐Lynch hereditary variants. Appropriate selection for expanded germline evaluation remains challenging. Case Presentation A 41‐year‐old man with locally advanced UTUC underwent neoadjuvant chemotherapy followed by surgery. His family history included gastrointestinal and breast cancers and did not fit a single hereditary syndrome. Although SSGT was initially considered for Lynch syndrome, germline MGPT was performed after genetic counseling. MGPT identified a germline pathogenic BRCA2 frameshift variant, with no mismatch repair gene variants detected. Conclusion This case highlights the value of comprehensive germline evaluation in selected UTUC patients. Urologists should recognize atypical/mixed family histories and consider early genetic referral. Selective MGPT may improve identification of clinically actionable germline variants.