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

Karin Anna Wallentin Wadt; L G Aoude; P Johansson; A Solinas; A Pritchard; O Crainic; M.T. Andersen; Jens Folke Kiilgaard; S Heegaard; L Sunde; Birgitte Federspiel; J Madore; J F Thompson; S W McCarthy; A Goodwin; H Tsao; G Jönsson; K Busam; R Gupta; J M Trent; A-M Gerdes; K M Brown; R A Scolyer; N K Hayward

doi:10.1111/cge.12501

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

Karin Anna Wallentin Wadt, L G Aoude, P Johansson, A Solinas, A Pritchard, O Crainic, M.T. Andersen, Jens Folke Kiilgaard, S Heegaard, L Sunde, Birgitte 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

62 Citations (Scopus)

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 language	English
Journal	Clinical Genetics
Volume	88
Issue number	3
Pages (from-to)	267-272
Number of pages	6
ISSN	0009-9163
DOIs	https://doi.org/10.1111/cge.12501
Publication status	Published - 1 Sept 2015

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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

Wadt, KAW, Aoude, LG, Johansson, P, Solinas, A, Pritchard, A, Crainic, O, Andersen, MT, Kiilgaard, JF , Heegaard, S, Sunde, L, Federspiel, B, Madore, J, Thompson, JF, McCarthy, SW, Goodwin, A, Tsao, H, Jönsson, G, Busam, K, Gupta, R, Trent, JM, Gerdes, A-M, Brown, KM, Scolyer, RA & Hayward, NK 2015, 'A recurrent germline BAP1 mutation and extension of the BAP1 tumor predisposition spectrum to include basal cell carcinoma', Clinical Genetics, vol. 88, no. 3, pp. 267-272. https://doi.org/10.1111/cge.12501

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

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.",

author = "Wadt, {Karin Anna Wallentin} and Aoude, {L G} and P Johansson and A Solinas and A Pritchard and O Crainic and M.T. Andersen and Kiilgaard, {Jens Folke} and S Heegaard and L Sunde and Birgitte Federspiel and J Madore and Thompson, {J F} and McCarthy, {S W} and A Goodwin and H Tsao and G J{\"o}nsson and K Busam and R Gupta and Trent, {J M} and A-M Gerdes and Brown, {K M} and Scolyer, {R A} and Hayward, {N K}",

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T1 - A recurrent germline BAP1 mutation and extension of the BAP1 tumor predisposition spectrum to include basal cell carcinoma

AU - Wadt, Karin Anna Wallentin

AU - Aoude, L G

AU - Johansson, P

AU - Solinas, A

AU - Pritchard, A

AU - Crainic, O

AU - Andersen, M.T.

AU - Kiilgaard, Jens Folke

AU - Heegaard, S

AU - Sunde, L

AU - Federspiel, Birgitte

AU - Madore, J

AU - Thompson, J F

AU - McCarthy, S W

AU - Goodwin, A

AU - Tsao, H

AU - Jönsson, G

AU - Busam, K

AU - Gupta, R

AU - Trent, J M

AU - Gerdes, A-M

AU - Brown, K M

AU - Scolyer, R A

AU - Hayward, N K

PY - 2015/9/1

Y1 - 2015/9/1

N2 - 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.

AB - 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.

U2 - 10.1111/cge.12501

DO - 10.1111/cge.12501

M3 - Journal article

C2 - 25225168

SN - 0009-9163

VL - 88

SP - 267

EP - 272

JO - Clinical Genetics

JF - Clinical Genetics

IS - 3

ER -

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

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