Jiang Jingjing, Liu Yujun
Department of Endocrinology and Metabolism, Zhongshan Hospital, Fudan University, China.
Department of Urology, Zhongshan Hospital, Fudan University, China.
Best Pract Res Clin Endocrinol Metab. 2024 Dec;38(6):101928. doi: 10.1016/j.beem.2024.101928. Epub 2024 Aug 23.
Pheochromocytomas and paragangliomas (PPGLs) represent the highest degree of heritability of any known tumor types in humans. Previous studies have characterized a dramatic difference between Chinese and European Caucasians with regards to both genetics and clinical features of PPGLs. The proportion of PGLs in Chinese patients was higher than in Caucasians, and the prevalence of metastasis was much lower in Chinese patients. Compared with Caucasians, there were more pathogenic variants (PVs) found in HRAS and FGFR1, but less in NF1 and SDHB. There were less germline PVs found in Chinese patients. Importantly, in Chinese patients, there was a large proportion of PGLs with PVs found in HRAS and FGFR1, mostly with epinephrine-producing capacity. This finding provided solid evidence that genetics (cluster 1 vs. 2), rather than location (PCC vs. PGL), determines the catecholamine-producing phenotype. Besides, the lower prevalence of SDHB partially explained lower occurrence of metastatic lesions in Chinese patients. These findings underscore the importance of considering ethnic differences when evaluating PPGLs and patient outcomes.
嗜铬细胞瘤和副神经节瘤（PPGLs）是人类已知肿瘤类型中遗传性最高的。先前的研究已经揭示，在PPGLs的遗传学和临床特征方面，中国患者与欧洲白种人之间存在显著差异。中国患者中副神经节瘤的比例高于白种人，且中国患者转移的发生率要低得多。与白种人相比，在HRAS和FGFR1中发现的致病变异（PVs）更多，而在NF1和SDHB中则较少。在中国患者中发现的胚系PVs较少。重要的是，在中国患者中，很大一部分副神经节瘤在HRAS和FGFR1中存在PVs，大多具有产生肾上腺素的能力。这一发现提供了确凿的证据，即遗传学（第1组与第2组）而非位置（嗜铬细胞瘤与副神经节瘤）决定了产生儿茶酚胺的表型。此外，SDHB较低的发生率部分解释了中国患者转移病变发生率较低的原因。这些发现强调了在评估PPGLs和患者预后时考虑种族差异的重要性。
