A BAP1 Mutation in a Danish Family Predisposes to Uveal Melanoma and Other Cancers

TY - JOUR

T1 - A BAP1 Mutation in a Danish Family Predisposes to Uveal Melanoma and Other Cancers

AU - Aoude, Lauren G.

AU - Wadt, Karin

AU - Bojesen, Anders

AU - Cruger, Dorthe

AU - Borg, Åke

AU - Trent, Jeffrey M.

AU - Brown, Kevin M.

AU - Gerdes, Anne-Marie

AU - Jönsson, Göran B

AU - Hayward, Nicholas K.

PY - 2013

Y1 - 2013

N2 - 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.

AB - 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.

U2 - 10.1371/journal.pone.0072144

DO - 10.1371/journal.pone.0072144

M3 - Article

C2 - 23977234

VL - 8

JO - PLoS ONE

JF - PLoS ONE

SN - 1932-6203

IS - 8

M1 - e72144

ER -