Department of Ophthalmology, The Ohio State University, Columbus, Ohio, USA.
J Med Genet. 2011 Dec;48(12):856-9. doi: 10.1136/jmedgenet-2011-100156. Epub 2011 Sep 22.
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.
研究胚系序列改变在具有遗传性癌症易感性的葡萄膜黑色素瘤（UM）患者中的潜在作用。
共研究了 53 名具有遗传性癌症高危风险的无血缘关系的 UM 患者和 1 名先证者的 5 名额外家族成员。通过直接测序进行突变筛查。
在所研究的 53 名 UM 患者中，发现 1 名患者存在胚系 BAP1 截断突变，c.799C→T(p.Q267X)，该突变在数名家族成员中存在，并与 UM 和其他癌症相关。在 3 名具有这种胚系 BAP1 突变的家族成员的 UM、肺腺癌和脑膜瘤肿瘤中，发现 BAP1 存在双等位基因失活和 BAP1 表达降低。在另外 2 名 UM 患者中还发现了胚系 BAP1 意义不明的变体，可能是非致病性的。
本研究报道了一种由胚系 BAP1 突变引起的新的遗传性癌症综合征，使患者易患 UM、肺癌、脑膜瘤，可能还有其他癌症。结果表明，BAP1 仅是遗传性 UM 的一小部分患者的候选基因，提示其他候选基因的存在。
