Mesothelioma patients with germline BAP1 mutations have 7-fold improved long-term survival.
BRCA1-associated protein-1 (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 with sporadic MM. We compared survival among germline BAP1 mutation MM patients with that of all MM (N = 10 556) recorded in the United States Surveillance, Epidemiology, and End Results (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 5 years, as compared with <1 year for the median survival in the United States SEER MM group. Five-year survival was 47%, 95% confidence interval (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 with 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 7-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.
University of Hawaii Cancer Center, Honolulu, HI 96813, USA, fbaumann@cc.hawaii.edu.
Francine
F
Baumann
University of Hawaii Cancer Center, Honolulu, HI 96813, USA.
Erin
E
Flores
University of Hawaii Cancer Center, Honolulu, HI 96813, USA, Department of Molecular Biosciences and Bioengineering, University of Hawaii at Mānoa, Honolulu, HI 96822, USA.
Andrea
A
Napolitano
Department of Biomedical Sciences, Samuel Oschin Comprehensive Cancer Institute-Cedars-Sinai, Los Angeles, CA 90048, USA.
Shreya
S
Kanodia
Department of Population Health, Hofstra-North Shore LIJ School of Medicine, Great Neck, NY 11021, USA and.
Emanuela
E
Taioli
Department of Cardiothoracic Surgery, New York University Langone Medical Center, New York, NY 10016, USA.
Harvey
H
Pass
University of Hawaii Cancer Center, Honolulu, HI 96813, USA.
Haining
H
Yang
University of Hawaii Cancer Center, Honolulu, HI 96813, USA, fbaumann@cc.hawaii.edu mcarbone@cc.hawaii.edu.
Michele
M
Carbone
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D016022:Case-Control Studies; D015331:Cohort Studies; D005260:Female; D005500:Follow-Up Studies; D020022:Genetic Predisposition to Disease; D018095:Germ-Line Mutation / Q000235:genetics*; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics* / Q000401:mortality; D008297:Male; D008654:Mesothelioma / Q000235:genetics* / Q000401:mortality; D000086002:Mesothelioma, Malignant; D008875:Middle Aged; D016609:Neoplasms, Second Primary / Q000235:genetics* / Q000401:mortality; D010534:Peritoneal Neoplasms / Q000235:genetics* / Q000401:mortality; D010997:Pleural Neoplasms / Q000235:genetics* / Q000401:mortality; D011379:Prognosis; D018426:SEER Program; D015996:Survival Rate; D025521:Tumor Suppressor Proteins / Q000235:genetics*; D043222:Ubiquitin Thiolesterase / Q000235:genetics*
C400134:BAP1 protein, human; D025521:Tumor Suppressor Proteins; D043222:Ubiquitin Thiolesterase