Clinical characteristics of patients with malignant pleural mesothelioma harboring somatic BAP1 mutations

Our plain-English summary of Clinical characteristics of patients with malignant pleural mesothelioma harboring somatic BAP1 mutations, by M.G. Zauderer, M. Bott, R. McMillan, et al (Journal of Thoracic Oncology, 2013).

The study

• Authors: M.G. Zauderer, M. Bott, R. McMillan, C.S. Sima, V. Rusch, L.M. Krug, M. Ladanyi
• Journal: Journal of Thoracic Oncology
• Published: 2013;8(11):1430-3
• Cited by: 70 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

Introduction: Genomic studies of malignant pleural mesothelioma (MPM) have recently identified frequent mutations in the BRCA-associated protein 1(BAP1) gene. In uveal melanoma and clear cell renal cell carcinoma, BAP1 mutations are associated with poor outcomes but their clinical significance in MPM is unknown. We therefore undertook this study to define the characteristics of patients whose MPM tumors harbor somatic BAP1 mutation and to examine the relationship between BAP1 mutation and survival.

Methods: We reviewed the charts of 121 patients with MPM tumors diagnosed between 1991 and 2009 tested for BAP1 mutation, and extracted the following information: age at diagnosis, sex, histology, stage, smoking status, asbestos exposure, family or personal history of malignancy, and treatment including surgery, chemotherapy, and radiation as well as survival status.

Results: Twenty-four of the 121 tumors (20%) harbored somatic BAP1 mutations. The percentage of current or former smokers among cases with BAP1 mutations was significantly higher than in BAP1 wild-type cases, (75% versus 42%; p = 0.006). However, the types of nucleotide substitutions in BAP1 did not suggest that this association was because of a causative role of smoking in BAP1 mutations. No other clinical feature was significantly different among those with and without BAP1 mutations in their MPM. There was also no difference in survival according to somatic BAP1 mutation status.

Conclusion: There is no apparent distinct clinical phenotype for MPM with somatic BAP1 mutation. The significance of the more frequent history of smoking among patients with BAP1-mutated MPM warrants further study.

In plain English

This brief report reviewed records of 121 Memorial Sloan-Kettering patients with malignant pleural mesothelioma. Their tumors, collected from 1991 to 2009, had been tested for mutations in the BAP1 gene. The mutations studied were somatic, meaning acquired in the tumor rather than inherited. Twenty-four of the 121 tumors (20%, 95% confidence interval 13% to 27%) carried a BAP1 mutation. Overall, 40% of patients reported known asbestos exposure. Former or current smoking was more common with BAP1-mutated tumors than without (75% versus 42%, p = 0.006). However, only two of the 14 point mutations were the type classically linked to smoking. Asbestos exposure, age, sex, stage, tumor type, treatment and cancer history did not differ significantly between groups. Median overall survival was 14.3 months (95% confidence interval 12.4 to 19.4) with a BAP1 mutation and 14.8 months (10.6 to 37.3) without (p = 0.81). The authors concluded there was no apparent distinct clinical phenotype for mesothelioma with somatic BAP1 mutation. They noted the retrospective design limited investigation of smoking and asbestos exposure, and therapy changes could have obscured survival differences.

We wrote this plain-English summary from the full article with the help of AI, and a second AI model checked each sentence against the article. It is not the authors' wording; the abstract and the article are their own account.

What the study did and found

• Design: Retrospective review of clinical records (brief report)
• Who was studied: 121 patients with malignant pleural mesothelioma at Memorial Sloan-Kettering Cancer Center, New York, whose tumor specimens were collected from 1991 to 2009 and selected based on availability of frozen tumor specimens from a surgical banking effort; median age 64, 70% men
• Exposure: The main factor studied was somatic BAP1 mutation in the tumor. Asbestos exposure was recorded only as known or not known (40% of all patients reported known exposure). No fiber types, products, jobs or doses are given. Smoking status and pack-years were also recorded.
• Main results:
  • 24 of 121 tumors (20%; 95% confidence interval 13% to 27%) harbored a somatic BAP1 mutation
  • Former or current smoking was more common among patients with BAP1-mutant tumors than among those with BAP1 wild-type tumors: 75% versus 42% (p = 0.006)
  • Among smokers, pack-years did not differ by BAP1 mutation status
  • Of the 14 point mutations among the 24 BAP1 mutations, only two were classic smoking-associated nucleotide transversions
  • In univariate analysis there was no significant difference between BAP1-mutant and BAP1 wild-type patients in age, sex, asbestos exposure, surgery, chemotherapy, radiation, family history of mesothelioma, family history of cancer, or personal history of cancer
  • There was no significant difference in stage at presentation (p = 0.43) between BAP1-mutant and wild-type disease
  • There was no difference in the distribution of histologies (p = 0.28) between BAP1-mutant and wild-type disease
  • Median overall survival was 14.3 months (95% CI, 12.4 to 19.4) for patients with BAP1-mutant tumors and 14.8 months (95% CI, 10.6 to 37.3) for patients with BAP1 wild-type tumors, p = 0.81. After adjustment for stage, p = 0.77.
• The authors' conclusion: The authors concluded that there is no apparent distinct clinical phenotype for malignant pleural mesothelioma with somatic BAP1 mutation
• Limitations the authors state:
  • The retrospective design precluded thorough investigation of smoking status, asbestos exposure, and personal and family history of cancer
  • Because specimens were obtained over an 18-year period, changes in therapy could have obscured survival differences by BAP1 mutation status

Topics

The National Library of Medicine indexes this study under subjects our site covers: Lung cancer, Mesothelioma.

Medical terms in this study, explained in our Lexicon: Pleural Mesothelioma, BAP1, Carcinoma, Histology, Asbestos Exposure, Chemotherapy.

Related studies

• Prevalence and Preliminary Validation of Screening Criteria to Identify Carriers of Germline BAP1 Mutations — M.G. Zauderer, G. Jayakumaran, et al. (2019)
• Prevalence of BRCA-1 associated protein 1 germline mutation in sporadic malignant pleural mesothelioma cases — A. Rusch, G. Ziltener, et al. (2015)
• Intrahepatic cholangiocarcinoma development in a patient with a novel BAP1 germline mutation and low exposure to asbestos — G. Brandi, M. Deserti, et al. (2020)
• Absence of germline mutations in BAP1 in sporadic cases of malignant mesothelioma — S. Sneddon, J.S. Leon, et al. (2015)
• Germline BAP1 mutations predispose to malignant mesothelioma — J.R. Testa, M. Cheung, et al. (2011)
• Germline BAP1 mutations predispose also to multiple basal cell carcinomas — A. de la Fouchardière, O. Cabaret, et al. (2015)

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