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

Karin A.W. Wadt, L. G. Aoude, P. Johansson, A. Solinas, A. Pritchard, O. Crainic, M. T. Andersen, J. F. Kiilgaard, S. Heegaard, L. Sunde, B. Federspiel, J. Madore, J. F. Thompson, S. W. Mccarthy, A. Goodwin, H. Tsao, G. Jönsson, K. Busam, R. Gupta, J. M. TrentA. M. Gerdes, K. M. Brown, R. A. Scolyer, N. K. Hayward

Research output: Contribution to journalArticle

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.

Original languageEnglish (US)
Pages (from-to)267-272
Number of pages6
JournalClinical Genetics
Volume88
Issue number3
DOIs
StatePublished - Sep 1 2015

Keywords

  • BAP1
  • BCC
  • Cancer predisposition syndrome
  • Germline mutation
  • Melanoma
  • Unknown primary tumor

ASJC Scopus subject areas

  • Genetics
  • Genetics(clinical)

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  • Cite this

    Wadt, K. A. W., Aoude, L. G., Johansson, P., Solinas, A., Pritchard, A., Crainic, O., Andersen, M. T., Kiilgaard, J. F., Heegaard, S., Sunde, L., Federspiel, B., Madore, J., Thompson, J. F., Mccarthy, S. W., Goodwin, A., Tsao, H., Jönsson, G., Busam, K., Gupta, R., ... Hayward, N. K. (2015). A recurrent germline BAP1 mutation and extension of the BAP1 tumor predisposition spectrum to include basal cell carcinoma. Clinical Genetics, 88(3), 267-272. https://doi.org/10.1111/cge.12501