Jiang Jingjing, Pang Yingxian, Luo Rongkui, Wei Yongbao, Zhang Jing, Li Minghao, Xu Yitong, Teng Xiaochun, Wu Hongmei, Guan Haixia, Wu Xiaohong, Yan Chenyan, Zhong Dewen, Deng Wanglong, Xu Ning, Wen Yanlin, Feng Yu, Yan Bin, Wang Long, Jiang Yazhuo, Ning Jinzhuo, Xu Xiaowen, Soria Miguel J, Robledo Mercedes, Pacak Karel, Liu Yujun, Liu Longfei
Department of Endocrinology and Metabolism, Zhongshan Hospital Fudan University, Shanghai, China.
Department of Urology, Xiangya Hospital, Central South University, 87 Xiangya Road, Changsha, 410008, Hunan, China.
J Endocrinol Invest. 2025 Apr;48(4):931-939. doi: 10.1007/s40618-024-02509-w. Epub 2024 Dec 5.
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.
嗜铬细胞瘤和副神经节瘤（PPGLs）在所有人类肿瘤中具有最高的遗传度，但膀胱副神经节瘤（UBPGLs）的遗传学仍知之甚少。本研究旨在探讨一组中国UBPGLs患者的特征，尤其关注遗传学方面。
该研究纳入了来自中国15个中心的70例中国UBPGLs患者、240例膀胱外非头颈部副神经节瘤（non-HNPGLs）患者以及16例高加索UBPGLs患者。肿瘤DNA样本通过下一代测序进行测序。所有鉴定出的致病变异（PVs）均通过桑格测序进行确认。
在70例中国患者中，38例鉴定出PVs：1A簇中有23例（13例SDHB、1例SDHD、1例SDHA、4例IDH1、2例SLC25A11和2例FH），1B簇中有4例（3例EPAS1和1例EGLN1），2类基因中有11例（7例HRAS、1例FGFR1、2例NF1和1例H3F3A）。与其他non-HNPGLs相比，UBPGLs在1A簇基因中的PVs更多（32.9%对14.2%，p<0.001），但在1B簇（5.7%对19.2%，p = 0.002）和2类基因中更少（15.7%对42.5%，p<0.001）。SDHB中的PVs（18.6%）在中国UBPGLs患者中最常见，其次是HRAS（10.0%）。在所有UBPGLs中，45.7%未发现PVs。在高加索UBPGLs患者中也鉴定出了HRAS、SLC25A11、EPAS1和FH中的PVs。
中国UBPGLs患者具有多样化的基因谱。1A簇基因中的PVs是近1/3患者的发病基础，突出了基因检测的重要性。高加索UBPGLs患者中也存在多种种系和体细胞PVs。
