A <i>BAP1</i> Mutation in a Danish Family Predisposes to Uveal Melanoma and Other Cancers

<div><p>Truncating germline mutations in the tumor suppressor gene BRCA-1 associated protein-1 (<i>BAP1</i>) 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 <i>BAP1</i> mutation suggesting a possible phenotypic characteristic of <i>BAP1</i> mutation carriers. Though there have been many types of cancer associated with germline <i>BAP1</i> 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 <i>BAP1</i> splice mutation located at c.581-2A>G, which leads to a premature truncation of <i>BAP1</i> 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 <i>BAP1</i> as an important uveal and cutaneous melanoma tumor suppressor gene and implicates its involvement in the development of lung, and stomach cancer.</p>