Prevalence of BRCA-1 associated protein 1 germline mutation in sporadic malignant pleural mesothelioma cases

Our plain-English summary of Prevalence of BRCA-1 associated protein 1 germline mutation in sporadic malignant pleural mesothelioma cases, by A. Rusch, G. Ziltener, K. Nackaerts, et al (Lung Cancer, 2015).

The study

• Authors: A. Rusch, G. Ziltener, K. Nackaerts, W. Weder, R.A. Stahel, E. Felley-Bosco
• Journal: Lung Cancer
• Published: 2015;87(1):77-9
• Cited by: 34 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

Objective: 23% of mesothelioma tumor specimens have a mutation in the BRCA1-associated protein 1 (BAP1) gene and germline BAP1 mutations predispose to malignant pleural mesothelioma (MPM). Our aim was to investigate germline BAP1 mutations in sporadic MPM patients.

Materials And Methods: Exonic DNA from peripheral blood leucocytes of 78 MPM patients was screened for germline BAP1 mutation.

Results: One out of 78 patients showed a germline synonymous mutation in exon 11. In all other patients wild-type sequence without any single-nucleotide polymorphisms was detected.

Conclusions: Taking into account previous similar screenings, the prevalence of germline BAP1 mutations in sporadic MPM patients can be estimated around 1-2%, suggesting a minor role of germline BAP1 mutation in the pathogenesis of sporadic MPM.

Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

In plain English

This study looked for inherited (germline) changes in the BAP1 gene in people with malignant pleural mesothelioma described as sporadic cases. The authors sequenced blood DNA from 78 patients in a multicenter clinical trial (SAKK 17/04), collected between 2008 and 2012. The trial included only stage I to III disease. There were 72 men and 6 women, and 69 of the tumors were epithelioid. The article does not report the patients' asbestos exposure. No non-synonymous germline BAP1 mutations, the kind that change the protein's amino-acid sequence, were detected. One patient carried a known synonymous variant in exon 11 that does not change the encoded amino acid. The authors said its relevance to tumor development remains to be explored. All other patients had the normal sequence. None of the 78 reported a history of uveal melanoma, an eye cancer. The authors combined their results with two earlier screenings, 113 patients in all. They estimated germline BAP1 mutations at around 1 to 2% of sporadic pleural mesothelioma patients, which they said suggests the mutation has a minor role in causing the disease.

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: Genetic screening study: blood DNA from mesothelioma patients was sequenced for inherited BAP1 gene changes. The journal labels it a case report, but it covers 78 patients.
• Who was studied: 78 patients with pathologically proven malignant pleural mesothelioma, stage I to III, from a multicenter clinical study (SAKK 17/04). Blood samples were collected between 2008 and 2012. There were 72 males and 6 females, with a median age of 61.2 years (SD plus or minus 6.1 years) at diagnosis.
• Exposure: The study did not report asbestos exposure or fiber types. What it examined was inherited (germline) changes in the BAP1 gene, found by sequencing all of the gene's coding regions in blood DNA.
• Main results:
  • Among the 78 patients, tumor types were 69 epithelioid (88.5%), 5 sarcomatoid (6.4%) and 4 biphasic (5.1%). Stages were 15 stage I (19.2%), 37 stage II (47.4%) and 26 stage III (33.3%).
  • No non-synonymous germline BAP1 mutation, meaning a mutation that changes the encoded amino-acid sequence, was found in any of the 78 patients.
  • One patient (patient 76) carried a known synonymous variant in exon 11 (rs71651686, c.1026C>T) that does not change the encoded amino acid. No alterations were found in any other sample.
  • The authors gave the frequency of this silent variant as 0.6% and said it was consistent with the frequency seen in the Swiss normal population.
  • None of the 78 patients reported a history of uveal melanoma.
• The authors' conclusion: The authors pooled their 78 patients with two earlier screenings, 113 patients in total. They estimated that the prevalence of germline BAP1 mutations in sporadic malignant pleural mesothelioma is around 1 to 2%. They wrote that the screenings to date suggest a minor role of germline BAP1 mutation in causing sporadic MPM. They also wrote that germline BAP1 testing must be considered in patients who report both asbestos exposure and past uveal melanoma, or when there is a familial predisposition syndrome.
• Limitations the authors state:
  • The authors said it is not yet known whether the synonymous variant found in one patient affects predisposition to tumors, since synonymous mutations can change protein expression, conformation and function.

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: Germline Mutation, Pleural Mesothelioma, Mesothelioma, BAP1, BAP1 Tumor Predisposition Syndrome.

Related studies

• Absence of germline mutations in BAP1 in sporadic cases of malignant mesothelioma — S. Sneddon, J.S. Leon, et al. (2015)
• Prevalence and Preliminary Validation of Screening Criteria to Identify Carriers of Germline BAP1 Mutations — M.G. Zauderer, G. Jayakumaran, et al. (2019)
• Analysis of BAP1 Germline Gene Mutation in Young Uveal Melanoma Patients — C.M. Cebulla, E.M. Binkley, 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)
• A recurrent germline BAP1 mutation and extension of the BAP1 tumor predisposition spectrum to include basal cell carcinoma — K.A. Wadt, L.G. Aoude, et al. (2015)

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