Germline BAP1 mutation predisposes to uveal melanoma, lung adenocarcinoma, meningioma, and other cancers.
Germline BAP1 mutation predisposes to uveal melanoma, lung adenocarcinoma, meningioma, and other cancers.
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DOI：
10.1136/jmedgenet-2011-100156
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发表时间：
2011-12
影响因子：
4
通讯作者：
Davidorf FH
中科院分区：
文献类型：
--
作者：
Abdel-Rahman MH;Pilarski R;Cebulla CM;Massengill JB;Christopher BN;Boru G;Hovland P;Davidorf FH
目的探讨葡萄膜黑色素瘤(UM)患者中BAP1基因种系序列改变与遗传性癌症易感性的关系。研究对象包括53名无血缘关系、遗传癌风险高的UM患者和另外5名先证者的家庭成员。用直接测序法进行突变筛查。在研究的53名UM患者中，有一名患者被确认为BAP1胚系截断突变c.799 C→T(p.Q267X)，该突变分离于几个家庭成员，与UM和其他癌症有关。在UM、肺腺癌和脑膜瘤中发现了BAP1的双等位基因失活和表达降低，这些肿瘤来自于三个带有该胚系BAP1突变的家庭成员。在另外两名UM患者中也发现了意义不确定的胚系BAP1变异，可能是非致病性的。这项研究报告了一种新的遗传性癌症综合征，由胚系BAP1突变引起，该突变使患者容易患上UM、肺癌、脑膜瘤，可能还有其他癌症。结果表明，在遗传性UM中，只有一小部分候选基因是BAP1，提示其他候选基因的作用。
To investigate the potential contribution of germline sequence alterations in the BAP1 gene in uveal melanoma (UM) patients with possible predisposition to hereditary cancer. A total of 53 unrelated UM patients with high risk for hereditary cancer and five additional family members of one proband were studied. Mutational screening was carried out by direct sequencing. Of the 53 UM patients studied, a single patient was identified with a germline BAP1 truncating mutation, c. 799 C→T (p.Q267X), which segregated in several family members and was associated with UM and other cancers. Biallelic inactivation of BAP1 and decreased BAP1 expression were identified in the UM, lung adenocarcinoma and meningioma tumours from three family members with this germline BAP1 mutation. Germline BAP1 variants of uncertain significance, likely non-pathogenic, were also identified in two additional UM patients. This study reports a novel hereditary cancer syndrome caused by a germline BAP1 mutation that predisposes patients to UM, lung carcinoma, meningioma, and possibly other cancers. The results indicate that BAP1 is the candidate gene in only a small subset of hereditary UM, suggesting the contribution of other candidate genes.
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DOI：
10.1126/science.1194472
发表时间：
2010-12-03
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Harbour JW;Onken MD;Roberson ED;Duan S;Cao L;Worley LA;Council ML;Matatall KA;Helms C;Bowcock AM
通讯作者：
Bowcock AM
BRCA1相关蛋白-1是一种需要去泛素化活性和核定位的肿瘤抑制剂。
影响因子：
11.2
作者：
Ventii KH;Devi NS;Friedrich KL;Chernova TA;Tighiouart M;Van Meir EG;Wilkinson KD
通讯作者：
Wilkinson KD
影响因子：
14.9
作者：
Hebsgaard, SM;Korning, PG;Brunak, S
通讯作者：
Brunak, S
影响因子：
11.2
作者：
Onken, MD;Worley, LA;Harbour, JW
通讯作者：
Harbour, JW
影响因子：
8
作者：
Jensen, DE;Proctor, M;Rauscher, FJ
通讯作者：
Rauscher, FJ