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Multicenter Study
. 2025 Apr;48(4):931-939.
doi: 10.1007/s40618-024-02509-w. Epub 2024 Dec 5.

Genetics of urinary bladder paragangliomas: a multi-center study of a Chinese cohort

Jingjing Jiang  1 , Yingxian Pang  2   3 , Rongkui Luo  4 , Yongbao Wei  5 , Jing Zhang  1 , Minghao Li  2   3 , Yitong Xu  6 , Xiaochun Teng  7 , Hongmei Wu  8 , Haixia Guan  9 , Xiaohong Wu  10 , Chenyan Yan  10 , Dewen Zhong  11 , Wanglong Deng  12 , Ning Xu  13 , Yanlin Wen  14 , Yu Feng  15 , Bin Yan  16 , Long Wang  17 , Yazhuo Jiang  18 , Jinzhuo Ning  19 , Xiaowen Xu  2   3 , Miguel J Soria  20 , Mercedes Robledo  21 , Karel Pacak  22 , Yujun Liu  23 , Longfei Liu  24   25
Affiliations
Multicenter Study

Genetics of urinary bladder paragangliomas: a multi-center study of a Chinese cohort

Jingjing Jiang et al. J Endocrinol Invest. 2025 Apr.

Abstract

Purpose: Pheochromocytomas and paragangliomas (PPGLs) exhibit the highest degree of heritability among all human tumors, yet the genetics of urinary bladder paragangliomas (UBPGLs) remains poorly understood. The present study aims to examine the characteristics of a cohort of Chinese patients with UBPGLs, focusing particularly on genetics.

Methods: The study included 70 Chinese patients with UBPGLs from 15 centers in China, 240 patients with non-head and neck PGLs (non-HNPGLs) outside the urine bladder, and 16 Caucasian patients with UBPGLs. Tumor DNA samples were sequenced by next generation sequencing. All identified pathogenic variants (PVs) were confirmed by Sanger sequencing.

Results: Among the 70 Chinese patients, PVs were identified in 38 cases: 23 in cluster 1 A (13 SDHB, 1 SDHD, 1 SDHA, 4 IDH1, 2 SLC25A11, and 2 FH), 4 in cluster 1B (3 EPAS1 and 1 EGLN1), and 11 in cluster 2 genes (7 HRAS, 1 FGFR1, 2 NF1, and 1 H3F3A). Compared with other non-HNPGLs, UBPGLs had more PVs in cluster 1 A genes (32.9% vs. 14.2%, p < 0.001), but fewer in cluster 1B (5.7% vs. 19.2%, p = 0.002) and cluster 2 genes (15.7% vs. 42.5%, p < 0.001). PVs in SDHB (18.6%) was the most common in Chinese patients with UBPGLs, followed by HRAS (10.0%). No PVs was found in 45.7% of all UBPGLs. PVs in HRAS, SLC25A11, EPAS1, and FH were also identified in Caucasians with UBPGLs.

Conclusion: Chinese patients with UBPGLs have a diverse genetic profile. PVs in cluster 1 A genes underlie nearly 1/3 of patients, highlighting the importance of genetic testing. Diverse germline and somatic PVs are also present in Caucasian patients with UBPGLs.

Keywords: SDHB; Pathogenic variants; Urinary bladder paragangliomas.

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Conflict of interest statement

Declaration. Conflict of interest: All authors have no conflict of interests to declare. Ethical approval and informed consent: The study adhered to the Declaration of Helsinki and Good Clinical Practice guidelines. Patients provided written informed consent for the utilization of their data and materials in clinical studies, in accordance with approvals from the respective Ethics Committee or Institutional Review Board (IRB) approvals in CNIO, NIH, and China.

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