Germline Multigene Panel Testing in Japanese Patients with Pheochromocytoma and Paraganglioma: Technical Feasibility and Clinical Utility.

Background

Pheochromocytoma and paraganglioma (PPGL) are rare neuroendocrine tumors with a high rate of germline predisposition. Although multigene panel testing (MGPT) using next-generation sequencing (NGS) is widely adopted globally, its clinical application in Japan remains limited.

Methods

We developed a custom amplicon-based NGS panel targeting 12 established PPGL susceptibility genes. Germline analysis was performed in 23 Japanese patients with confirmed PPGL to evaluate sequencing quality and variant detection.

Results

Sequencing quality was consistently high (Q30 > 96%, mapping rate >99%, on-target rate >80%), with nearly all exons (148/149) achieving >1,000× coverage. Pathogenic or likely pathogenic variants were found in 21.7% (5/23), including SDHB, VHL, and RET. In addition, variants of uncertain significance (VUS) were found in 17.4% (4/23), including novel missense variants in FH, SDHA, and MAX.

Conclusions

This study demonstrates the feasibility and clinical utility of amplicon-based MGPT for PPGL in a real-world Japanese setting and highlights the importance of ongoing VUS reclassification to improve clinical interpretation. The findings support its diagnostic value, reflect underlying clinical demand, and contributed to its non-insured clinical adoption at certified laboratories in Japan.