Hereditary Mutations in BAP1 Gene Raise Risk of Mesothelioma ► NCI Cancer Bulletin for September 6, 2011 - National Cancer Institute

Hereditary Mutations in BAP1 Gene Raise Risk of Mesothelioma

In two independent studies, researchers have shown that people with hereditary mutations in a gene known as BAP1 are predisposed to develop malignant mesothelioma and melanoma of the eye (uveal or intraocular melanoma), and a distinctive type of benign skin tumor. The findings, published online August 28 in Nature Genetics, suggest that inherited BAP1 mutations may also be linked to some other forms of cancer, including melanoma of the skin.
In one study, supported by NCI, a team of investigators led by Dr. Joseph Testa of the Fox Chase Cancer Center and Dr. Michele Carbone of the University of Hawaii Cancer Center focused on two U.S. families with a high incidence of mesothelioma. The study is the first to show that inherited gene mutations can influence a person’s risk of mesothelioma—one of the least curable forms of cancer. Mesothelioma is typically associated with exposure to asbestos or to a similar mineral fiber, erionite.
The second study, led by Drs. Thomas Wiesner of the Medical University of Graz, Austria, and Memorial Sloan-Kettering Cancer Center (MSKCC); Boris Bastian of MSKCC; and Michael Speicher, also of the Medical University of Graz, focused on two families, one from Germany and one from Austria, in which members developed numerous small, benign skin growths starting at an early age. These raised growths occurred in pigment-producing cells called melanocytes but were skin-colored, unlike typical moles.
In both studies, researchers zeroed in on the BAP1 gene after finding genetic changes in or near the region of human chromosome 3 where BAP1 is located. The BAP1 gene encodes a protein known as BRCA1-associated protein-1, which is found in the cell nucleus and is thought to suppress tumors. The BAP1 protein has been implicated in a range of cellular processes, including regulation of cell growth and division and response to DNA damage.
In the two families with mesothelioma, Drs. Testa, Carbone, and their colleagues found BAP1 mutations in two individuals with uveal melanoma, one of whom subsequently developed mesothelioma. The research team also found hereditary alterations in BAP1 in 2 of 26 patients with sporadic mesothelioma. Both individuals had previously been diagnosed with uveal melanoma, although none of the other 24 patients had. Some of the patients with sporadic mesothelioma were found to have noninherited BAP1 alterations in their tumors.
Their findings, Drs. Testa and Carbone wrote, “suggest that individuals with uveal melanoma who carry [hereditary] BAP1 mutations are at high risk of developing mesothelioma and should be closely monitored."
In each family that Dr. Wiesner and his colleagues studied, one individual with benign skin tumors also had melanoma of the eye. In addition, three members of one family were diagnosed with skin melanoma. These investigators also found noninherited BAP1 mutations in randomly selected tumors from an independent group of patients with melanoma of the eye and skin.
In two other recent studies (here and here), noninherited mutations in BAP1 were found in tumor tissue of sporadic cases of mesothelioma and melanoma of the eye.
NCI Cancer Bulletin for September 6, 2011 - National Cancer Institute: - Enviado mediante la barra Google