Germline SDHB mutations and familial renal cell carcinoma
Germline SDHB mutations and familial renal cell carcinoma
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DOI：
10.1093/jnci/djn254
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发表时间：
2008-09-03
期刊：
影响因子：
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通讯作者：
Maher, Eamonn R.
中科院分区：
文献类型：
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作者：
Ricketts, Christopher;Woodward, Emma R.;Maher, Eamonn R.
家族性肾细胞癌（RCC）是一种异质性疾病，最常由VHL、MET和FLCN基因的种系突变或3号染色体易位引起。然而，对于许多家族性肾细胞癌患者，疾病的遗传基础尚不明确。我们研究了富马酸水合酶（FH）或琥珀酸脱氢酶亚基基因（SDHB， SDHC， SDHD）的种系突变是否与RCC易感性相关，在68例没有临床证据的RCC易感性综合征患者中。先显子中未发现FH、SDHC或SDHD突变，但68个先显子中有3个（4.4%）存在种系SDHB突变。种系SDHB突变的患者表现为家族性RCC （n = 1）或双侧RCC (n = 2)，没有嗜铬细胞瘤或头颈部副神经节瘤的个人或家族史。SDHB突变携带者的RCC诊断年龄从24岁到73岁不等。这些发现1)表明，疑似遗传性RCC患者应进行种系SDHB突变检查，2)建议所有已确定的SDHB突变携带者都应进行RCC监测，3)提供家族性RCC与缺氧基因反应途径激活之间的进一步联系。
Familial renal cell carcinoma (RCC) is a heterogeneous disorder that is most commonly caused by germline mutations in the VHL, MET, and FLCN genes or by constitutional chromosome 3 translocations. However, for many patients with familial RCC, the genetic basis of the disease is undefined. We investigated whether germline mutations in fumarate hydratase ( FH) or succinate dehydrogenase subunit genes ( SDHB, SDHC, SDHD) were associated with RCC susceptibility in 68 patients with no clinical evidence of an RCC susceptibility syndrome. No mutations in FH, SDHC, or SDHD were identified in probands, but 3 of the 68 (4.4%) probands had a germline SDHB mutation. Patients with a germline SDHB mutation presented with familial RCC (n = 1) or bilateral RCC (n = 2) and no personal or family history of pheochromocytoma or head and neck paraganglioma. Age at diagnosis of RCC in SDHB mutation carriers ranged from 24 to 73 years. These findings 1) demonstrate that patients with suspected inherited RCC should be examined for germline SDHB mutations, 2) suggest that all identified SDHB mutation carriers should be offered surveillance for RCC, and 3) provide a further link between familial RCC and activation of hypoxic-gene response pathways.