Le Guin Claudia Helga Dorothee, Metz Klaus Alfred, Kreis Stefan Horst, Bechrakis Nikolaos Emmanouel, Bornfeld Norbert, Zeschnigk Michael, Lohmann Dietmar Rudolf
Department of Ophthalmology, University Hospital Essen, University Duisburg-Essen, Hufelandstr. 55, 45147 Essen, Germany.
Department of Pathology, University Hospital Essen, University Duisburg-Essen, Hufelandstr. 55, 45147 Essen, Germany.
Cancers (Basel). 2019 Jul 22;11(7):1031. doi: 10.3390/cancers11071031.
Several tumors, including uveal melanoma, show somatic mutations of . Circumscribed choroidal hemangioma is a benign tumor that becomes symptomatic in adulthood. In some patients, morphologic examination of biopsies is required for differential diagnosis between amelanotic choroidal melanoma and circumscribed choroidal hemangioma. Here, we report the results of mutation analysis in samples from circumscribed choroidal hemangioma. Deep amplicon sequencing (Illumina MiSeq, San Diego, CA, USA) of positions R183 and Q209 of GNAQ and GNA11 in tissue samples from 33 patients with histologically diagnosed circumscribed choroidal hemangioma. All patients underwent biopsy or enucleation at our clinic between 2008 and 2018. To enable detection of variant alleles at low fractions, read depth exceeded 15,000-fold. DNA for genetic analysis was prepared from either snap-frozen (n = 22) or FFPE (n = 11) tissue samples. Samples from 28/33 patients (85%) showed a somatic missense mutation of GNAQ (c.626 A > G) predicted to result in p.Q209R. Variant allele fraction was variable (range 2.3% to 28%). Variants of GNAQ resulting in p.Q209 are characteristic for circumscribed choroidal hemangiomas. It appears that the GNAQ mutation spectrum in this tumor is narrow, possibly restricted to p.Q209R. Moreover, the spectrum is distinct from that of uveal melanoma, in which alterations resulting in p.Q209R are very rare.
包括葡萄膜黑色素瘤在内的几种肿瘤显示出……的体细胞突变。局限性脉络膜血管瘤是一种良性肿瘤，在成年期出现症状。在一些患者中，活检的形态学检查对于无色素性脉络膜黑色素瘤和局限性脉络膜血管瘤的鉴别诊断是必需的。在此，我们报告了局限性脉络膜血管瘤样本的……突变分析结果。对33例经组织学诊断为局限性脉络膜血管瘤患者的组织样本中GNAQ和GNA11基因的R183和Q209位点进行深度扩增子测序（美国加利福尼亚州圣地亚哥的Illumina MiSeq）。所有患者在2008年至2018年期间在我们诊所接受了活检或眼球摘除术。为了能够检测低比例的变异等位基因，读取深度超过15000倍。用于基因分析的DNA由速冻组织样本（n = 22）或福尔马林固定石蜡包埋组织样本（n = 11）制备。33例患者中的28例（85%）样本显示GNAQ基因的体细胞错义突变（c.626 A > G），预测导致p.Q209R。变异等位基因比例各不相同（范围为2.3%至28%）。导致p.Q209的GNAQ变异是局限性脉络膜血管瘤的特征。看来该肿瘤中GNAQ突变谱较窄，可能仅限于p.Q209R。此外，该谱与葡萄膜黑色素瘤不同，在葡萄膜黑色素瘤中导致p.Q209R的改变非常罕见。
