A study investigating the frequency of BAP1 mutations in the germline of asbestos-exposed patients with mesothelioma and a family history of cancer reported that the mutations were found in 6 percent of the individuals, and associated with an earlier age of cancer development but also better prognosis.
Mutations in this tumor suppressor gene have been associated with an increased risk of mesothelioma and other cancers, but it was not known how frequent these mutations are in patients with a family history of cancer.
The research team, led by Jill A. Ohar from the Wake Forest University School of Medicine, screened 150 asbestos-exposed mesothelioma patients with a family history of cancer, as well as two groups of control individuals — 50 persons that had been exposed to asbestos and had a family of non-mesothelioma cancers, and 153 asbestos-exposed individuals with no family history of cancer.
The article, “Germline BAP1 Mutational Landscape of Asbestos-Exposed Malignant Mesothelioma Patients with Family History of Cancer,” appeared in the journal Cancer Research .
The team found BAP1 mutations in nine out of the 150 mesothelioma patients, constituting 6 percent of the group. The mutations present in these individuals were of varying types, including missense mutations — where a change in a base-pair of the DNA sequence results in the production of another amino acid — and frameshift mutations, where insertion or deletion of DNA bases causes an error in how the sequence is read.
The identified missense mutations led to a decreased enzyme activity of BAP1. The team also noticed that mutation carriers developed mesothelioma at a younger age and showed better long-term survival compared to mesothelioma patients without the mutations.
The cancers found in the BAP1 carriers more often developed in the peritoneum, which forms the lining of the abdominal cavity, rather than in the pleural cavity of the lungs.
Many tumors harboring the BAP1 germline mutations were also associated with BAP1 cancer syndrome. That syndrome is characterized by the development of multiple cancers, including mesothelioma, ocular and cutaneous melanomas, as well as renal, breast, lung, gastric, and basal cell carcinomas.
The study reported that no BAP1 mutations were found in the control patients.
The findings point to the importance of genetic testing of mesothelioma patients presenting with a family history of cancer. Individuals with BAP1 mutations might benefit from further screening and routine monitoring to allow for early detection and intervention.