Germline HABP2 Mutation Causing Familial Nonmedullary Thyroid Cancer.
Germline HABP2 Mutation Causing Familial Nonmedullary Thyroid Cancer.
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DOI：
10.1056/nejmoa1502449
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发表时间：
2015-07-30
期刊：
影响因子：
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通讯作者：
Kebebew E
中科院分区：
文献类型：
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作者：
Gara SK;Jia L;Merino MJ;Agarwal SK;Zhang L;Cam M;Patel D;Kebebew E
家族性非髓样甲状腺癌占所有甲状腺癌病例的3 - 9%，但其易感基因尚不清楚。在这里，我们报告了HABP 2的种系变异在7个家族性非髓样甲状腺癌的亲属和4.7%的423例甲状腺癌患者中的受影响成员。与正常邻近甲状腺组织和散发性癌症样本相比，这种变异与受影响家族成员肿瘤样本中HABP 2蛋白表达增加相关。功能研究表明，HABP 2具有肿瘤抑制作用，而G534 E变体导致功能丧失。
Familial nonmedullary thyroid cancer accounts for 3 to 9% of all cases of thyroid cancer, but the susceptibility genes are not known. Here, we report a germline variant of HABP2 in seven affected members of a kindred with familial nonmedullary thyroid cancer and in 4.7% of 423 patients with thyroid cancer. This variant was associated with increased HABP2 protein expression in tumor samples from affected family members, as compared with normal adjacent thyroid tissue and samples from sporadic cancers. Functional studies showed that HABP2 has a tumor-suppressive effect, whereas the G534E variant results in loss of function.