Format

Send to

Choose Destination
Clin Genet. 2015 Sep;88(3):267-72. doi: 10.1111/cge.12501. Epub 2014 Nov 6.

A recurrent germline BAP1 mutation and extension of the BAP1 tumor predisposition spectrum to include basal cell carcinoma.

Author information

1
Department of Clinical Genetics, Rigshospitalet, Copenhagen, Denmark.
2
QIMR Berghofer Medical Research Institute, Genetics and Computational Biology, Brisbane, Australia.
3
University of Queensland, Brisbane, Australia.
4
Tissue Pathology and Diagnostic Oncology, Royal Prince Alfred Hospital, Sydney, Australia.
5
Department of Ophthalmology, Glostrup Hospital, University of Copenhagen, Copenhagen, Denmark.
6
Eye Pathology Institute, Department of Neuroscience and Pharmacology, University of Copenhagen, Copenhagen, Denmark.
7
Department of Clinical Genetics, Aarhus University Hospital, Aarhus, Denmark.
8
Department of Pathology, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark.
9
Melanoma Institute Australia, North Sydney, Australia.
10
Sydney Medical School, The University of Sydney, Sydney, Australia.
11
Department of Cancer Genetics, Royal Prince Alfred Hospital, Sydney, Australia.
12
Department of Dermatology, Massachusetts General Hospital, Boston, MA, USA.
13
Department of Clinical Sciences Lund, Division of Oncology, Lund University, Lund, Sweden.
14
Memorial Sloan-Kettering Cancer Center, New York, NY, USA.
15
Translational Genomics Research Institute, Phoenix, AZ, USA.
16
Laboratory of Translational Genomics, National Cancer Institute, Bethesda, MD, USA.

Abstract

We report four previously undescribed families with germline BRCA1-associated protein-1 gene (BAP1) mutations and expand the clinical phenotype of this tumor syndrome. The tumor spectrum in these families is predominantly uveal malignant melanoma (UMM), cutaneous malignant melanoma (CMM) and mesothelioma, as previously reported for germline BAP1 mutations. However, mutation carriers from three new families, and one previously reported family, developed basal cell carcinoma (BCC), thus suggesting inclusion of BCC in the phenotypic spectrum of the BAP1 tumor syndrome. This notion is supported by the finding of loss of BAP1 protein expression by immunochemistry in two BCCs from individuals with germline BAP1 mutations and no loss of BAP1 staining in 53 of sporadic BCCs consistent with somatic mutations and loss of heterozygosity of the gene in the BCCs occurring in mutation carriers. Lastly, we identify the first reported recurrent mutation in BAP1 (p.R60X), which occurred in three families from two different continents. In two of the families, the mutation was inherited from a common founder but it arose independently in the third family.

KEYWORDS:

BAP1; BCC; cancer predisposition syndrome; germline mutation; melanoma; unknown primary tumor

PMID:
25225168
DOI:
10.1111/cge.12501
[Indexed for MEDLINE]

Supplemental Content

Full text links

Icon for Wiley
Loading ...
Support Center