Department of Ophthalmology, University of Helsinki and Helsinki University Hospital, Helsinki, Finland; Folkhälsan Institute of Genetics, Helsinki, Finland.
Folkhälsan Institute of Genetics, Helsinki, Finland.
Ophthalmology. 2016 May;123(5):1112-7. doi: 10.1016/j.ophtha.2016.01.008. Epub 2016 Feb 12.
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.
Cohort study.
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.
Sequencing BAP1.
Pathogenic variants in BAP1.
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.
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.
BRCA1 相关蛋白-1 基因（BAP1）的种系突变使携带者易患葡萄膜黑色素瘤。我们报告了生活在该癌症高发地区的芬兰葡萄膜黑色素瘤患者中 BAP1 种系致病性变异的基于人群的频率。
队列研究。
在芬兰，葡萄膜黑色素瘤在赫尔辛基大学医院的眼部肿瘤科中心治疗。我们从 2010 年 1 月至 2012 年 12 月连续诊断的 188 名患者中收集了临床数据和基因组 DNA。其中 7 名患者来自 6 个家族，1 名亲属有葡萄膜黑色素瘤病史，另外 2 名患者来自 2 个额外的家族，2 名亲属均有该病史。
对 BAP1 进行测序。
BAP1 中的致病性变异。
我们在 3 名患者中发现了 BAP1 中的 2 种不同的致病性变异。2 名患者在 14 号外显子中发生单个核苷酸插入，导致阅读框移位。这两名患者都有至少 1 名亲属有葡萄膜黑色素瘤病史。1 名无葡萄膜黑色素瘤家族史的患者在 2 号内含子的保守剪接供体位点发生了单个核苷酸替换。所有 3 个家族均存在 BAP1 癌症易感性综合征相关癌症。BAP1 致病性变异的总体频率为 2.0%（148 例患者中有 3 例；95%置信区间，0.4-5.8），50 岁及以下患者的频率为 3.6%（28 例患者中有 1 例；95%置信区间，0.1-18），在 8 个有葡萄膜黑色素瘤病史的家族中有 2 个家族发现了致病性变异。
来自该癌症高发地区的芬兰葡萄膜黑色素瘤连续患者中 BAP1 种系致病性变异的频率与其他人群的报告相当。
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