The Importance of Multidisciplinary Approach in Early Detection of BAP1 Tumor Predisposition Syndrome: Clinical Management and Risk Assessment

Our plain-English summary of The Importance of Multidisciplinary Approach in Early Detection of BAP1 Tumor Predisposition Syndrome: Clinical Management and Risk Assessment, by A. Battaglia (Clinical Medicine Insights. Oncology, 2014).

The study

• Author: A. Battaglia
• Journal: Clinical Medicine Insights. Oncology
• Published: 2014;8:37-47
• Type of article: Review
• Cited by: 39 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

Germline BAP1 (BRCA1-associated protein-1) mutations are involved into a novel specific cancer syndrome and strictly associated with a high cancer susceptibility. Recent data suggest that BAP1 has activity toward target substrates explaining why loss of BAP1 causes a pro-tumorigenic deregulation of gene expression. The recently published data reviewed raise the hypothesis that BAP1 regulates a common subset of substrates, which in turn causes a pro-tumorigenic deregulation of gene expression, and alternatively suggest the role of BAP1 as tumorigenesis suppressor/promoter also by independent mechanisms. The clinical phenotype of BAP1 alterations includes MBAITs (melanocytic BAP1-mutated atypical intradermal tumors), uveal melanoma (UM), cutaneous melanoma (CM), renal cell carcinoma (RCC), mesothelioma (MM), and possibly several other tumors. In clinical practice, early diagnosis is crucial for curative resection of all these tumor types. The uniformed and unambiguous definition of MBAITs as clinical/pathological predictive markers could provide physicians means to identify patients who may carry germline BAP1 mutations and thus could be at high risk of developing CM, UM, MM, RCC, and possibly other tumors. As part of a novel multidisciplinary approach, physicians, pathologists, and clinicians involved into diagnostics should be aware of the histological features and the spectrum of tumors associated with BAP1 loss. Further clinical, epidemiological, and functional studies are required to fully explain the roles of BAP1 and its interaction partners in neoplasia, to define mechanisms behind shared and non-shared clinical and pathological criteria.

In plain English

This article was a review by a single author at the University of Catania, Italy, of published research on BAP1. The author described inherited (germline) mutations in this gene as causing a cancer predisposition syndrome. The review covered how the BAP1 protein works in cells, the types of BAP1 mutations reported, and the tumors linked to them. These were uveal melanoma, cutaneous melanoma, renal cell carcinoma, mesothelioma, skin tumors called MBAITs, and possibly others. It summarized an earlier analysis by Carbone and colleagues that compared 63 people with BAP1 mutations to 55 without. That analysis reported overall cancer prevalence of 63.5% in the mutated group and 9.1% in the non-mutated group. A table in the review listed malignant mesothelioma "after asbestos exposure" as a feature of the syndrome. The review gave no new data on asbestos and named no fiber types. The author proposed a three-step multidisciplinary detection approach and suggested that knowing a carrier's asbestos exposure history could help assess mesothelioma risk. The author concluded that MBAITs could serve as markers for identifying possible carriers. The author noted a lack of consensus among pathologists, and that screening costs, risks and benefits were not yet fully established.

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: narrative review of published literature
• Who was studied: No new participants; the author reviewed published studies and reported cases of BAP1 mutations, including families and individuals with germline BAP1 mutations
• Exposure: Germline (inherited) and somatic BAP1 gene mutations. Asbestos exposure is mentioned only as a context for mesothelioma in a table and in the prevention discussion; no fiber types or doses are given.
• Main results:
  • The review reported an earlier pooled analysis by Carbone et al. of 63 BAP1-mutated and 55 non-mutated individuals. Overall cancer prevalence was 63.5% in the BAP1-mutated cohort and 9.1% in the non-mutated cohort (P less than 0.001).
  • In that earlier analysis, as reported in the review, the prevalence of mesothelioma, uveal melanoma, cutaneous melanoma and MBAITs was significantly higher in the BAP1-mutated cohort.
  • The review's table of syndrome features listed malignant mesothelioma after asbestos exposure.
  • The review reported an earlier screening study (Pilarski et al.) of 46 unrelated uveal melanoma patients plus 4 additional patients. That study found 3 patients with germline pathogenic BAP1 mutations.
  • The author proposed a three-step multidisciplinary approach for early detection of the syndrome.
  • The author suggested that identifying carriers with a personal history of asbestos exposure could help evaluate their risk of mesothelioma.
• The authors' conclusion: The author concluded that a uniform, shared definition of MBAITs/ASTs as clinical and pathological markers could help physicians identify people who may carry germline BAP1 mutations and be at high risk of cutaneous melanoma, uveal melanoma, mesothelioma, renal cell carcinoma and possibly other tumors.
• Limitations the authors state:
  • Pathologists do not agree on MBAITs as a marker or on its nomenclature.
  • Cost efficiency of screening and its risks and benefits were not yet fully established.
  • The findings do not exclude other genes contributing to hereditary predisposition.
  • Further clinical, pathological and correlation studies are needed before MBAITs can be used as an early clinical marker.

Topics

Medical terms in this study, explained in our Lexicon: Multidisciplinary Team, BAP1 Tumor Predisposition Syndrome, BAP1, Carcinogenesis, Carcinoma, Mesothelioma.

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