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

in Journal of endocrinological investigation by Jingjing Jiang, Yingxian Pang, Rongkui Luo, Yongbao Wei, Jing Zhang, Minghao Li, Yitong Xu, Xiaochun Teng, Hongmei Wu, Haixia Guan, Xiaohong Wu, Chenyan Yan, Dewen Zhong, Wanglong Deng, Ning Xu, Yanlin Wen, Yu Feng, Bin Yan, Long Wang, Yazhuo Jiang, Jinzhuo Ning, Xiaowen Xu, Miguel J Soria, Mercedes Robledo, Karel Pacak, Yujun Liu, Longfei Liu

TLDR

  • The study examined the genetics of urinary bladder paragangliomas (UBPGLs) in Chinese patients, identifying diverse pathogenic variants and highlighting the importance of genetic testing.
  • Compared to other non-HNPGLs, UBPGLs had a unique genetic profile, with a higher prevalence of PVs in cluster 1A genes.

Abstract

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. 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. 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. 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.

Overview

  • The study aims to examine the characteristics of a cohort of Chinese patients with urinary bladder paragangliomas (UBPGLs), focusing on genetics.
  • The study included 70 Chinese patients with UBPGLs, 240 patients with non-head and neck PGLs (non-HNPGLs), and 16 Caucasian patients with UBPGLs.
  • The primary objective of the study is to identify pathogenic variants (PVs) in Chinese patients with UBPGLs and compare them with those from non-HNPGLs and Caucasians with UBPGLs.

Comparative Analysis & Findings

  • Among the 70 Chinese patients, PVs were identified in 38 cases, with the most common being SDHB (18.6%) and HRAS (10.0%).
  • Compared to other non-HNPGLs, UBPGLs had more PVs in cluster 1A genes (32.9% vs. 14.2%, p < 0.001) and fewer in cluster 1B and cluster 2 genes.
  • Diverse germline and somatic PVs were also present in Caucasian patients with UBPGLs, including HRAS, SLC25A11, EPAS1, and FH.

Implications and Future Directions

  • The study highlights the importance of genetic testing, as PVs in cluster 1A genes underlie nearly 1/3 of Chinese patients with UBPGLs.
  • Future studies should focus on identifying the genetic causes of UBPGLs, as well as the potential therapeutic implications of these findings.
  • The study also underscores the need for further research to understand the genetic characteristics of UBPGLs in different ethnic populations.
Read Full Article