Oncogenomics Laboratory, Queensland Institute of Medical Research, Brisbane, Queensland, Australia ; University of Queensland, Brisbane, Queensland, Australia.
PLoS One. 2013 Aug 19;8(8):e72144. doi: 10.1371/journal.pone.0072144. eCollection 2013.
Truncating germline mutations in the tumor suppressor gene BRCA-1 associated protein-1 (BAP1) have been reported in families predisposed to developing a wide range of different cancer types including uveal melanoma and cutaneous melanoma. There has also been an association between amelanotic tumor development and germline BAP1 mutation suggesting a possible phenotypic characteristic of BAP1 mutation carriers. Though there have been many types of cancer associated with germline BAP1 mutation, the full spectrum of disease association is yet to be ascertained. Here we describe a Danish family with predominantly uveal melanoma but also a range of other tumor types including lung, neuroendocrine, stomach, and breast cancer; as well as pigmented skin lesions. Whole-exome sequencing identified a BAP1 splice mutation located at c.581-2A>G, which leads to a premature truncation of BAP1 in an individual with uveal melanoma. This mutation was carried by several other family members with melanoma or various cancers. The finding expands on the growing profile of BAP1 as an important uveal and cutaneous melanoma tumor suppressor gene and implicates its involvement in the development of lung, and stomach cancer.
已在易患多种不同癌症类型（包括葡萄膜黑色素瘤和皮肤黑色素瘤）的家族中报道了肿瘤抑制基因 BRCA-1 相关蛋白-1 (BAP1) 的种系截短突变。无黑色素性肿瘤的发生与种系 BAP1 突变之间也存在关联，提示 BAP1 突变携带者可能存在某种表型特征。尽管已有许多种癌症与种系 BAP1 突变相关，但疾病关联的全貌仍有待确定。在这里，我们描述了一个丹麦家族，该家族主要患有葡萄膜黑色素瘤，但也患有多种其他肿瘤类型，包括肺癌、神经内分泌癌、胃癌和乳腺癌；以及色素性皮肤病变。外显子组测序鉴定出一个位于 c.581-2A>G 的 BAP1 剪接突变，该突变导致一个患有葡萄膜黑色素瘤的个体中 BAP1 的过早截断。该突变被其他几个患有黑色素瘤或各种癌症的家族成员携带。这一发现扩展了 BAP1 作为一个重要的葡萄膜和皮肤黑色素瘤肿瘤抑制基因的作用，并暗示其参与了肺癌和胃癌的发展。
