Germline mutations in BAP1 predispose to melanocytic tumors

Area of Science:

• Oncology
• Genetics
• Dermatology

Background:

• Common acquired melanocytic nevi are benign skin growths.
• A new autosomal dominant syndrome presents with multiple, elevated melanocytic tumors.

Purpose of the Study:

• To identify the genetic basis of a novel syndrome causing multiple melanocytic tumors.
• To investigate the role of BAP1 mutations in familial and sporadic melanocytic neoplasms.

Main Methods:

• Described two families with the novel syndrome.
• Performed histopathological analysis of melanocytic neoplasms.
• Conducted genetic analysis to identify mutations in BAP1.
• Examined somatic alterations in BAP1 in sporadic tumors.

Main Results:

• Identified inactivating germline mutations in BAP1 segregating with the syndrome.
• Melanocytic neoplasms showed features ranging from epithelioid nevi to atypical proliferations with melanoma overlap.
• Affected individuals developed uveal or cutaneous melanomas.
• Loss of the wild-type BAP1 allele occurred through somatic alterations in most neoplasms.
• Found BAP1 mutations in a subset of sporadic melanocytic neoplasms with similar histology.

Conclusions:

• Loss of BAP1 function is associated with a distinct type of melanocytic neoplasm.
• BAP1 mutations contribute to the development of both familial and sporadic melanocytic tumors.
• This syndrome increases the risk of developing uveal and cutaneous melanomas.