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BAP1 germline mutations in Finnish uveal melanoma patients
Author(s) -
TURUNEN J,
MARKKINEN S,
WILSKA R,
MUONA M,
RAIVIO V,
TÄLL M,
LINDH S,
LEHESJOKI AE,
KIVELÄ T
Publication year - 2014
Publication title -
acta ophthalmologica
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.534
H-Index - 87
eISSN - 1755-3768
pISSN - 1755-375X
DOI - 10.1111/j.1755-3768.2014.4242.x
Subject(s) - bap1 , germline mutation , melanoma , exon , frameshift mutation , germline , mutation , medicine , cancer , cancer syndrome , cancer research , gene , oncology , genetics , biology
Abstract Purpose To estimate the frequency of germline mutations in the BRCA‐1 associated protein‐1 (BAP1) gene that predisposes to a range of cancer types, including uveal melanoma. Methods In Finland, all uveal melanoma patients are referred to the Ocular Oncology Service, Helsinki University Central Hospital. We collected clinical data and genomic DNA from 146 patients treated between 2011 and 2013. In addition, we identified 12 families each with two uveal melanoma patients. We were able to collect genomic DNA from 14 members of uveal melanoma families. All 17 exons of the BAP1 gene were sequenced in a total of 160 patients. Results We found two possible dominant mutations: a sporadic mutation in a highly conserved donor splice site after exon 2 and a frameshift insertion mutation in exon 14 in three patients. The latter mutation was found in a mother and son both diagnosed with uveal melanoma. The third patient, who shared the same mutation, is potentially a distant relative of this family. These mutations were not present in 3,325 Finnish controls from the Sisu project (www.sisuproject.fi). Conclusion BAP1 germline mutations in Finland contribute to uveal melanoma in only 1.4% of patients (2 mutations, 147 patients; 95% CI 0.2 ‐ 4.8) based on our non‐selected sample, excluding second cases in families. The BAP1 syndrome exists but does not seem to be particularly prevalent in Finland in spite that Northern Europe is a high risk region for this cancer.