BAP1 Germline Mutations in Finnish Patients with Uveal Melanoma

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• 作者：Joni A. Turunen ; MD ; PhD¹ ; ² ; ^&lowast ; ; ^{joni.turunen@helsinki.fi" class="auth_mail" title="E-mail the corresponding author} ; Salla Markkinen ; MSc² ; ^&lowast ; ; Rosi Wilska ; MD¹ ; Silva Saarinen ; MD ; PhD³ ; Virpi Raivio ; MD ; PhD¹ ; Martin T&auml ; ll ; MD¹ ; Anna-Elina Lehesjoki ; MD ; PhD² ; ⁴ ; Tero T. Kivel&auml ; MD ; PhD¹
• 关键词：BAP1 ; BRCA1-associated protein-1 ; BRCA1 ; breast cancer 1 ; CI ; confidence interval ; ExAC ; Exome Aggregation Consortium ; LBD ; largest basal diameter ; TNM ; Tumor ; Node ; Metastasis classification ; UCSC ; University of California Santa Cruz
• 刊名：Ophthalmology
• 出版年：2016
• 出版时间：May 2016
• 年：2016
• 卷：123
• 期：5
• 页码：1112-1117
• 全文大小：714 K

文摘

Germline mutations of the BRCA1-associated protein-1 gene (BAP1) predispose carriers to uveal melanoma. We report the population-based frequency of germline pathogenic variants of BAP1 in Finnish patients with uveal melanoma who live in a high-risk region for this cancer.

Design

Cohort study.

Participants

In Finland, uveal melanomas are treated centrally in the Ocular Oncology Service, Helsinki University Hospital. We collected clinical data and genomic DNA from 148 of 188 consecutive patients diagnosed from January 2010 through December 2012. Seven of these patients from 6 families had a history of uveal melanoma in 1 relative, and 2 patients from 2 additional families had such a history in 2 relatives.

Methods

Sequencing BAP1.

Main Outcome Measures

Pathogenic variants in BAP1.

Results

We found 2 different pathogenic variants in BAP1 in 3 patients. Two patients had a single nucleotide insertion in exon 14 resulting in a shift of reading frame. Both had a family history of uveal melanoma in at least 1 relative. One patient without a family history of uveal melanoma had a single nucleotide substitution in the conserved splice donor site of intron 2. BAP1 cancer predisposition syndrome-related cancers were present in all 3 families. The overall frequency of BAP1 pathogenic variants was 2.0% (3/148; 95% confidence interval, 0.4–5.8), the frequency among patients 50 years of age or younger was 3.6% (1/28; 95% confidence interval, 0.1–18), and a pathogenic variant was detected in 2 of 8 families with a history of uveal melanoma.

Conclusions

The frequency of BAP1 germline pathogenic variants in consecutive Finnish patients with uveal melanoma who come from a high-risk region for the development of this cancer is comparable with reports from other populations.