Germline mutations in BAP1 predispose to melanocytic tumors

被引：529

作者：

Wiesner, Thomas ^{[1
,2
]}

Obenauf, Anna C. ^{[3
,4
]}

Murali, Rajmohan ^{[2
]}

Fried, Isabella ^{[1
]}

Griewank, Klaus G. ^{[2
]}

Ulz, Peter ^{[3
]}

Windpassinger, Christian ^{[3
]}

Wackernagel, Werner ^{[5
]}

Loy, Shea ^{[2
]}

Wolf, Ingrid ^{[1
]}

Viale, Agnes ^{[6
]}

Lash, Alex E. ^{[7
]}

Pirun, Mono ^{[7
]}

Socci, Nicholas D. ^{[7
]}

Ruetten, Arno

Palmedo, Gabriele

Abramson, David ^{[8
]}

Offit, Kenneth ^{[4
,9
]}

Ott, Arthur ^{[10
]}

Becker, Juergen C. ^{[1
]}

Cerroni, Lorenzo ^{[1
]}

Kutzner, Heinz

Bastian, Boris C. ^{[2
,11
]}

Speicher, Michael R. ^{[3
]}

机构：

[1] Med Univ Graz, Dept Dermatol, Graz, Austria

[2] Mem Sloan Kettering Canc Ctr, Human Oncol & Pathogenesis Program, New York, NY 10021 USA

[3] Med Univ Graz, Inst Human Genet, Graz, Austria

[4] Mem Sloan Kettering Canc Ctr, Canc Biol & Genet Program, New York, NY 10021 USA

[5] Med Univ Graz, Dept Ophthalmol, Graz, Austria

[6] Mem Sloan Kettering Canc Ctr, Genom Core Lab, New York, NY 10021 USA

[7] Mem Sloan Kettering Canc Ctr, Computat Biol Ctr, New York, NY 10021 USA

[8] Mem Sloan Kettering Canc Ctr, Dept Surg, New York, NY 10021 USA

[9] Mem Sloan Kettering Canc Ctr, Clin Genet Serv, New York, NY 10021 USA

[10] Med Univ Graz, Inst Pathol, Graz, Austria

[11] Mem Sloan Kettering Canc Ctr, Dept Pathol, New York, NY 10021 USA

来源：

NATURE GENETICS | 2011年 / 43卷 / 10期

基金：

奥地利科学基金会; 美国国家卫生研究院;

关键词：

PROTEIN FUNCTION; UVEAL MELANOMA; CANCER; BREAST; NEVI;

D O I：

10.1038/ng.910

中图分类号：

Q3 [遗传学];

学科分类号：

071007 [遗传学];

摘要：

Common acquired melanocytic nevi are benign neoplasms that are composed of small, uniform melanocytes and are typically present as flat or slightly elevated pigmented lesions on the skin. We describe two families with a new autosomal dominant syndrome characterized by multiple, skin-colored, elevated melanocytic tumors. In contrast to common acquired nevi, the melanocytic neoplasms in affected family members ranged histopathologically from epithelioid nevi to atypical melanocytic proliferations that showed overlapping features with melanoma. Some affected individuals developed uveal or cutaneous melanomas. Segregating with this phenotype, we found inactivating germline mutations of BAP1, which encodes a ubiquitin carboxy-terminal hydrolase. The majority of melanocytic neoplasms lost the remaining wild-type allele of BAP1 by various somatic alterations. In addition, we found BAP1 mutations in a subset of sporadic melanocytic neoplasms showing histological similarities to the familial tumors. These findings suggest that loss of BAP1 is associated with a clinically and morphologically distinct type of melanocytic neoplasm.

引用

页码：1018 / U163

页数：5

共 17 条

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