Department of Otolaryngology, Head and Neck Surgery, Keio University School of Medicine, Tokyo, Japan.
Division of Hearing and Balance Research, National Institute of Sensory Organs, National Hospital Organization Tokyo Medical Center, Tokyo, Japan.
Clin Genet. 2023 Apr;103(4):466-471. doi: 10.1111/cge.14294. Epub 2023 Jan 14.
Carotid body tumor (CBT) is classified as a paraganglioma (PGL). Here, we report the genetic background, protein expression pattern, and clinical findings of 30 Japanese CBT cases. Germline pathogenic or likely pathogenic (P/LP) variants of genes encoding succinate dehydrogenase subunits (SDHs) were detected in 15 of 30 cases (50%). The SDHB variants were the most frequently detected, followed by SDHA and SDHD variants. One case with SDHAF2 variant was bilateral CBT, and other two multiple PGL cases were not detected P/LP variants. The three cases with germline variants that could be tested did not have somatic P/LP variants of the same genes. Immunohistochemical analysis showed negative SDHB signals in CBT tissues in five cases with germline P/LP variants of SDHB, SDHD, or SDHA. In addition, SDHB signals in CBT tissues were negative in four of nine cases without germline P/LP variants of SDHs. These findings suggest the involvement of unidentified molecular mechanisms affecting SDHs.
颈动脉体肿瘤 (CBT) 被归类为副神经节瘤 (PGL)。在这里，我们报告了 30 例日本 CBT 病例的遗传背景、蛋白表达模式和临床发现。在 30 例中的 15 例 (50%) 检测到编码琥珀酸脱氢酶亚基 (SDH) 的基因的种系致病性或可能致病性 (P/LP) 变异。SDHB 变异是最常检测到的，其次是 SDHA 和 SDHD 变异。一例具有 SDHAF2 变异的双侧 CBT，另外两例多发性 PGL 病例未检测到 P/LP 变异。可检测的三个具有种系变异的病例没有相同基因的体细胞 P/LP 变异。免疫组织化学分析显示，在 5 例具有 SDHB、SDHD 或 SDHA 种系 P/LP 变异的 CBT 组织中，SDHB 信号为阴性。此外，在 9 例无 SDH 种系 P/LP 变异的 CBT 组织中，有 4 例 SDHB 信号为阴性。这些发现表明存在影响 SDH 的未识别分子机制。
