Cheung Mitchell, Kadariya Yuwaraj, Talarchek Jacqueline, Pei Jianming, Ohar Jill A, Kayaleh Omar R, Testa Joseph R
Cancer Biology Program and Genomics Facility, Fox Chase Cancer Center, Philadelphia, PA 19111, USA.
Section of Pulmonary, Critical Care, Allergy and Immunologic Diseases, Wake Forest University School of Medicine, Winston-Salem, NC 27157-1054, USA.
Cancer Lett. 2015 Dec 28;369(2):261-5. doi: 10.1016/j.canlet.2015.09.011. Epub 2015 Sep 26.
We report a high-risk cancer family with multiple mesotheliomas, cutaneous melanomas, basal cell carcinomas, and meningiomas segregating with a germline nonsense mutation in BAP1 (c.1938T>A; p.Y646X). Notably, most (four of five) mesotheliomas were peritoneal rather than the usually more common pleural form of the disease, and all five mesothelioma patients also developed second or third primary cancers, including two with meningiomas. Another family member developed both cutaneous melanoma and breast cancer. Two family members had basal cell carcinomas, and six others had melanocytic tumors, including four cutaneous melanomas, one uveal melanoma, and one benign melanocytic tumor. The family resides in a subtropical area, and several members had suspected exposure to asbestos either occupationally or in the home. We hypothesize that the concurrence of a genetic predisposing factor and environmental exposure to asbestos and UV irradiation contributed to the high incidence of multiple cancers seen in this family, specifically mesothelioma and various uveal/skin tumors, respectively.
我们报告了一个高危癌症家族，该家族中有多例间皮瘤、皮肤黑色素瘤、基底细胞癌和脑膜瘤，这些癌症与BAP1基因的种系无义突变（c.1938T>A；p.Y646X）共分离。值得注意的是，大多数（五例中的四例）间皮瘤是腹膜间皮瘤，而非该病通常更常见的胸膜间皮瘤形式，并且所有五例间皮瘤患者还发生了第二或第三种原发性癌症，其中两例患有脑膜瘤。另一名家庭成员同时患皮肤黑色素瘤和乳腺癌。两名家庭成员患有基底细胞癌，另外六名家庭成员患有黑素细胞肿瘤，包括四例皮肤黑色素瘤、一例葡萄膜黑色素瘤和一例良性黑素细胞肿瘤。该家族居住在亚热带地区，几名家庭成员怀疑在职业或家中接触过石棉。我们推测，遗传易感因素与石棉和紫外线辐射的环境暴露共同作用，导致了该家族中多种癌症的高发病率，特别是分别导致了间皮瘤和各种葡萄膜/皮肤肿瘤的高发。
