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While a cure for mesothelioma does not exist currently, doctors are working tirelessly to gain a greater understanding of genetic cues that can potentially lead to a cure for mesothelioma. Understanding genetic cues, like genomic mutations, can inform doctors of how mesothelioma develops in patients, which could lead to earlier detection of the disease and creation of individualized treatments for improved prognoses for patients.
The BAP1 mutation has been studied and identified as a marker for an increased likelihood of mesothelioma development in people exposed to asbestos, while also being a marker for increased survival time in mesothelioma patients. The BAP1 mutation assists both the growth and suppression of cancer cells, and it’s these insights that can lead to dramatic advances in mesothelioma treatment.
Families with a high risk for mesothelioma often harbored a BAP1 mutation in their genome.1 “A BAP1 mutation in your genome” or “genomic BAP1 mutation” means that all cells of the body contain the BAP1 mutation. In contrast, some patients have mesothelioma cancer cells that contain the BAP1 mutation but the rest of the person’s cells contain an active and healthy BAP1 protein.
Dr. Testa from Fox Chase Cancer Center (Philadelphia, PA) predicts that scientists can use this BAP1 mutation to “help identify individuals at high risk for mesothelioma who could be targeted for early intervention.”1
For example, family members of mesothelioma patients from North Dakota, especially those living along the gravel roads releasing the asbestos-like fibers called erionite2 may benefit from checking their BAP1 gene status.
People with BAP1 mutations in their genome also have a higher risk for melanomas (a deadly, rapidly spreading skin cancer) and basal cell carcinoma (a very common but slow growing skin cancer).3 Dr. de la Fouchardiere (Lyon, France) recommends that dermatologists should check for both types of skin cancer, as they belong to the BAP1 cancer syndrome.3
BAP1 helps repair DNA
The BAP1 gene produces an enzyme called deubiquinylase, one of 100 such enzymes that help control the activity, location, and breakdown of most proteins in cells. BAP1 and three other enzymes act on similar type bonds.
After DNA damage, BAP1 recruits a complex of DNA repair proteins and RNA. This complex acts as master cabinet makers that fix the double strand breaks in DNA,4 which can be caused by ultraviolet light and asbestos, among other irritants.
Thus BAP1 is very important in cell repair.
Mesothelioma patients with genomic BAP1 mutations live 7 times longer than other mesothelioma patients
Dr. Francine Baumann and colleagues examined the length of survival, called overall survival, of mesothelioma patients with BAP1 mutations in their genome.5 The rare mesothelioma patients with genomic BAP1 mutations —all 23 of them that they had identified over the years -- had long survival times: half of these mesothelioma patients lived 10 years! Eleven of them are still alive. The age of the patients, gender, and the location of the tumors did not affect the overall survival. That is, patients with mesothelioma in the pleural cavity (chest) or the peritoneal cavity (abdomen) survived 5-10 years.
Survival of patients with mesothelioma for “5 years or more is exceedingly rare yet we observed it in more than half of mesothelioma patients with germline BAP1 mutations” stated Dr. Baumann.
Dr. Baumann, Carbone, and colleagues compared the survival of this rare group of mesothelioma patients to 10,556 mesothelioma patients in the large US database.5 Surprisingly, the mesothelioma patients that carry BAP1 mutations in their genome actually live approximately 7 times longer than mesothelioma patients with normal BAP1.5
Why? Those answers are being pursued and may lead to treatments for mesothelioma patients in the future.
Testa JR, Cheung M, Pei J et al. Germline BAP1 mutations predispose to malignant mesothelioma. Nat Genet 2011;43(10):1022-1025.
Carbone M, Baris YI, Bertino P et al. Erionite exposure in North Dakota and Turkish villages with mesothelioma. Proc Natl Acad Sci U S A 2011;108(33):13618-13623.
de la Fouchardiere A, Cabaret O, Savin L et al. Germline BAP1 mutations predispose also to multiple basal cell carcinomas. Clin Genet 2014.
Ismail IH, Davidson R, Gagne JP, Xu ZZ, Poirier GG, Hendzel MJ. Germline mutations in BAP1 impair its function in DNA double-strand break repair. Cancer Res 2014;74(16):4282-4294.
Baumann F, Flores E, Napolitano A et al. Mesothelioma patients with germline BAP1 mutations have 7-fold improved long-term survival. Carcinogenesis 2014.