Carcinogenesis 2014 November 7 [Epub ahead of print] [Link]
Baumann F, Flores E, Napolitano A, Kanodia S, Taioli E, Pass H, Yang H, Carbone M.
BAP1 mutations cause a new cancer syndrome, with a high rate of malignant mesothelioma (MM). Here, we tested the hypothesis that MM associated with germline BAP1 mutations has a better prognosis compared to sporadic MM. We compared survival among germline BAP1 mutation MM patients with that of all MM (N = 10 556) recorded in the US SEER data from 1973 to 2010. We identified 23 MM patients -11 alive- with germline BAP1 mutations and available data on survival. Ten patients had peritoneal MM, ten pleural MM, and three MM in both locations. Thirteen patients had one or more malignancies in addition to MM. Actuarial median survival for the MM patients with germline BAP1 mutations was five years, as compared with less than one year for the median survival in the US SEER MM group. Five-year survival was 47%, 95%CI [24-67%], as compared with 6.7% [6.2-7.3%] in the control SEER group. Analysis of the pooled cohort of germline BAP1 mutation MM showed that patients with peritoneal MM (median survival of 10 years, P=0.0571), or with a second malignancy in addition to MM (median survival of 10 years, P=0.0716), survived for a longer time compared to patients who only had pleural MM, or MM patients without a second malignancy, respectively. In conclusion, we found that MM patients with germline BAP1 mutations have an overall seven-fold increased long-term survival, independently of sex and age. Appropriate genetic counseling and clinical management should be considered for MM patients who are also BAP1 mutation carriers.