Ocular melanoma and the BAP1 hereditary cancer syndrome: implications for the dermatologist

Our plain-English summary of Ocular melanoma and the BAP1 hereditary cancer syndrome: implications for the dermatologist, by L.M. Martorano, R.R. Winkelmann, C.M. Cebulla, et al (International Journal of Dermatology, 2014).

The study

• Authors: L.M. Martorano, R.R. Winkelmann, C.M. Cebulla, M.H. Abdel-Rahman, S.M. Campbell
• Journal: International Journal of Dermatology
• Published: 2014;53(6):657-63
• Type of article: Review
• Cited by: 9 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

Ocular melanoma is a rare subtype of melanoma, which includes uveal melanoma (UM) and conjunctival melanoma. UM is associated with an increased risk of cutaneous melanoma (CM) in addition to mesothelioma, skin lesions such as epithelioid atypical Spitz tumors, and other internal malignancies due to a germline mutation of the BRCA1-associated protein 1 (BAP1) gene. Such familial risks are important for dermatologists to recognize when screening patients with a history of UM for CM and other malignancies. Molecular genetics further help to elucidate the connections between UM and CM by revealing similarities and differences in important mutations among the melanoma subtypes. Both UM and CM have been shown to harbor germline mutation of BAP1. However, somatic mutations in either GNAQ or GNA11 are unique to UM tumors and could be used as potential markers to differentiate UM from metastatic CM and act as direct therapeutic targets. However, CM-associated BRAF and CDKN2A mutations are rare in UM. This review addresses the clinical features, pathogenesis, and current treatment options of UM, focusing on UM and the BAP1 cancer syndrome to raise awareness of ocular melanoma and its greater role in the predisposition to a hereditary cancer syndrome.

© 2014 The International Society of Dermatology.

In plain English

This article was a review written for dermatologists. It covered ocular melanoma, mainly uveal melanoma (melanoma inside the eye), and an inherited cancer syndrome caused by germline (inherited) mutations of the BAP1 gene. It reported no new patient data and summarized earlier studies. The review stated that people with germline BAP1 mutations have an increased predisposition to uveal melanoma, cutaneous (skin) melanoma, epithelioid atypical Spitz tumors (a type of skin growth), mesothelioma, meningioma, lung adenocarcinoma and other internal cancers. It described this as a new autosomal dominant hereditary cancer syndrome. Citing earlier work, it reported that somatic (tumor-acquired, not inherited) BAP1 mutations had been identified in 84% of metastasizing uveal melanomas. Germline BAP1 mutations had been detected in a small subset of uveal melanoma patients. The review did not say whether the mesothelioma was pleural or peritoneal, and it did not discuss asbestos. The authors concluded that patients with uveal melanoma are at higher risk of skin melanoma and other internal cancers. They related these risks to inherited defects of the BAP1 gene and possibly to other genes not yet discovered.

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
• Who was studied: No study population of its own; the review drew on published literature about patients with uveal melanoma, cutaneous melanoma and germline BAP1 mutations
• Exposure: No asbestos exposure was discussed. The review concerned germline mutations of the BAP1 gene, plus other genetic changes in uveal melanoma.
• Main results:
  • The review stated that patients with germline BAP1 mutations have an increased predisposition to uveal melanoma, cutaneous melanoma, epithelioid atypical Spitz tumors, mesothelioma (type not specified), meningioma, lung adenocarcinoma and other internal malignancies
  • The review described this as a new autosomal dominant hereditary cancer syndrome
  • Citing an earlier study, somatic (tumor-acquired) inactivating BAP1 mutations had been identified in 84% of metastasizing uveal melanomas
  • Citing earlier studies, germline BAP1 mutations had been detected in a small subset of patients with uveal melanoma
  • The review stated that penetrance of the germline BAP1 mutation is lower in patients with cutaneous melanoma than in patients with uveal melanoma
  • Citing earlier studies, a significantly higher frequency of cutaneous melanoma was found in uveal melanoma patients than in the general population, and five of a cohort of 207 ocular melanoma patients developed primary cutaneous melanoma
• The authors' conclusion: The authors concluded that patients with uveal melanoma are at higher risk of developing cutaneous melanoma and other internal malignancies. They stated that these risks are related to inherited defects of the BAP1 gene and possibly to other genes not yet discovered.

Topics

Medical terms in this study, explained in our Lexicon: BAP1, Mesothelioma, Epithelioid, Germline Mutation, Somatic Mutation, CDKN2A, BAP1 Tumor Predisposition Syndrome.

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