Mutations in the SDHB gene are associated with extra-adrenal and/or malignant phaeochromocytomas.
Mutations in the SDHB gene are associated with extra-adrenal and/or malignant phaeochromocytomas.
复制标题
SDHB 基因突变与肾上腺外和/或恶性嗜铬细胞瘤有关。
作者：
A. Gimenez;J. Favier;P. Rustin;C. Rieubland;Malvina Crespin;V. Nau;P. Khau Van Kien;P. Corvol;P. Plouin;X. Jeunemaître
编码琥珀酸脱氢酶复合物亚基 B (SDHB) 和 D (SDHD) 的基因的种系突变已在家族性副神经节瘤和明显散发的嗜铬细胞瘤 (ASP) 中报道，但这些突变的基因型-表型关系尚不清楚。对 84 名 ASP 患者（除 2 名外均随访 8.8 +/- 5.7 年）（57 名患有肾上腺肿瘤，27 名患有肾上腺外、多发性、恶性或复发性肿瘤）筛查了嗜铬细胞瘤的主要易感基因（RET、VHL、SDHD 和 SDHB）。三十三个肿瘤可用于分子分析、酶测定和免疫组织化学。未检测到 RET (0%) 突变和 2 个 (2.4%) VHL 突变。在 6 名患者（7%）中仅发现 SDHD 基因中的两个编码单核苷酸多态性（G12S 和 H50R）。相反，在 8 名患者 (9.5%) 中发现了 SDHB 基因中的 6 个有害突变。异位部位和复发或恶性肿瘤与 SDHB 突变密切相关（8 例中有 7 例，87%；76 例中有 20 例，26%；P = 0.001）。体细胞 DNA 分析表明，33 例中有 16 例 (48%) 染色体 1p36（SDHB 位点）杂合性丢失。在所有具有 SDHB 突变的肿瘤中都发现 SDHB 基因座杂合性丧失，呼吸链酶检测显示复合物 II 催化活性完全丧失。具有 SDHB 突变的肿瘤的血管结构表现出典型的恶性肿瘤特征。这些数据强烈表明SDHB基因是一种抑癌基因，ASP患者中SDHB基因种系突变的鉴定应被视为恶性肿瘤或复发的高危因素。
Germ-line mutations in the genes encoding succinate dehydrogenase complex subunits B (SDHB) and D (SDHD) have been reported in familial paragangliomas and apparently sporadic phaeochromocytomas (ASP), but the genotype-phenotype relationships of these mutations are unknown. Eighty-four patients (all but 2 followed up for 8.8 +/- 5.7 years) with ASP (57 with adrenal tumors, 27 with extra-adrenal, multiple, malignant, or recurrent tumors) were screened for the major susceptibility genes for phaeochromocytoma (RET, VHL, SDHD, and SDHB). Thirty-three tumors were available for molecular analysis, enzyme assays, and immunohistochemistry. No (0%) RET and 2 (2.4%) VHL mutations were detected. Only two coding single nucleotide polymorphisms in the SDHD gene (G12S and H50R) were found in 6 patients (7%). Conversely, six deleterious mutations in the SDHB gene were identified in 8 patients (9.5%). Ectopic site and recurrence or malignancy were strongly associated with SDHB mutations (7 of 8, 87%, versus 20 of 76, 26%; P = 0.001). Somatic DNA analysis indicated a loss of heterozygosity at chromosome 1p36 (SDHB locus) in 16 of 33 cases (48%). A loss of heterozygosity at the SDHB locus was found in all tumors with SDHB mutation, and assays of respiratory chain enzymes showed a complete loss of complex II catalytic activity. The vascular architecture of tumors with SDHB mutations displayed features typical of malignancy. These data strongly suggest that SDHB gene is a tumor suppressor gene and that the identification of germ-line mutations in SDHB gene in patients with ASPs should be considered as a high-risk factor for malignancy or recurrence.
影响因子：
56.9
作者：
Baysal, BE;Ferrell, RE;Devlin, B
通讯作者：
Devlin, B