Maria Chiara Gelmi, Laurien E Houtzagers, Annemijn P A Wierenga, Mieke Versluis, Bastiaan T Heijmans, Gregorius P M Luyten, Peter de Knijff, Marije Te Raa, Rick H de Leeuw, Martine J Jager
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Clinical and histopathologic tumour characteristics, tumour chromosome status, and patient survival were compared among patients with different genotypes.</p><p><strong>Subjects: </strong>392 patients who underwent enucleation for UM at the Leiden University Medical Center, Leiden, The Netherlands.</p><p><strong>Methods: </strong>We isolated DNA from peripheral blood leukocytes of 392 patients with UM and performed sequencing, using six eye colour SNPs from the HIrisPlex-S assay. The genotypes extracted from the sequencing data were uploaded onto the Hirisplex webtool (https://hirisplex.erasmusmc.nl/) for eye colour prediction. We tested the association of eye colour SNPs with tumour characteristics and chromosome aberrations using Pearson's chi-square test and Mann-Whitney U test and survival with Kaplan-Meier curves with log-rank test and Cox regression.</p><p><strong>Main outcome measures: </strong>UM-related survival.</p><p><strong>Results: </strong>Of the total cohort of 392 patients with analysable genotype data, 307 (78%) were assigned to have blue eyes, 74 (19%) brown eyes and 11 (3%) could not be assigned to either blue or brown. Patients with a genetically-blue eye colour had a worse survival (p = 0.04). This was related to one genotype: patients with the G/G genotype of rs12913832 (HERC2) which codes for blue eye colour had a worse prognosis (p = 0.017), which was related to more often having high-risk tumours (monosomy of chromosome 3, p = 0.04) than patients with an A/G or A/A genotype.</p><p><strong>Conclusion: </strong>The G/G genotype of rs12913832 (HERC2), which is related to blue eye colour, is not only a genetic factor related to the risk to develop a UM, but is also linked to a worse prognosis, due to an association with a higher risk of developing a high-risk UM (carrying monosomy of chromosome 3).</p>","PeriodicalId":19533,"journal":{"name":"Ophthalmology","volume":null,"pages":null},"PeriodicalIF":13.1000,"publicationDate":"2024-09-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Survival in uveal melanoma patients is linked to genetic variation at HERC2 SNP rs12913832.\",\"authors\":\"Maria Chiara Gelmi, Laurien E Houtzagers, Annemijn P A Wierenga, Mieke Versluis, Bastiaan T Heijmans, Gregorius P M Luyten, Peter de Knijff, Marije Te Raa, Rick H de Leeuw, Martine J Jager\",\"doi\":\"10.1016/j.ophtha.2024.09.001\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Purpose: </strong>Uveal melanoma (UM) is a rare disease, with the highest incidence in people with a fair skin and light eyes. Eye colour is largely genetically determined and defined by a set of single nucleotide polymorphisms (SNPs). We set out to determine whether we could identify a SNP that is related to prognosis.</p><p><strong>Design: </strong>We sequenced DNA from peripheral blood mononuclear cells of 392 patients with UM and obtained the genotype of six common eye colour-related SNPs. Clinical and histopathologic tumour characteristics, tumour chromosome status, and patient survival were compared among patients with different genotypes.</p><p><strong>Subjects: </strong>392 patients who underwent enucleation for UM at the Leiden University Medical Center, Leiden, The Netherlands.</p><p><strong>Methods: </strong>We isolated DNA from peripheral blood leukocytes of 392 patients with UM and performed sequencing, using six eye colour SNPs from the HIrisPlex-S assay. The genotypes extracted from the sequencing data were uploaded onto the Hirisplex webtool (https://hirisplex.erasmusmc.nl/) for eye colour prediction. We tested the association of eye colour SNPs with tumour characteristics and chromosome aberrations using Pearson's chi-square test and Mann-Whitney U test and survival with Kaplan-Meier curves with log-rank test and Cox regression.</p><p><strong>Main outcome measures: </strong>UM-related survival.</p><p><strong>Results: </strong>Of the total cohort of 392 patients with analysable genotype data, 307 (78%) were assigned to have blue eyes, 74 (19%) brown eyes and 11 (3%) could not be assigned to either blue or brown. Patients with a genetically-blue eye colour had a worse survival (p = 0.04). This was related to one genotype: patients with the G/G genotype of rs12913832 (HERC2) which codes for blue eye colour had a worse prognosis (p = 0.017), which was related to more often having high-risk tumours (monosomy of chromosome 3, p = 0.04) than patients with an A/G or A/A genotype.</p><p><strong>Conclusion: </strong>The G/G genotype of rs12913832 (HERC2), which is related to blue eye colour, is not only a genetic factor related to the risk to develop a UM, but is also linked to a worse prognosis, due to an association with a higher risk of developing a high-risk UM (carrying monosomy of chromosome 3).</p>\",\"PeriodicalId\":19533,\"journal\":{\"name\":\"Ophthalmology\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":13.1000,\"publicationDate\":\"2024-09-06\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Ophthalmology\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1016/j.ophtha.2024.09.001\",\"RegionNum\":1,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"OPHTHALMOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Ophthalmology","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1016/j.ophtha.2024.09.001","RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"OPHTHALMOLOGY","Score":null,"Total":0}
引用次数: 0
摘要
目的:葡萄膜黑色素瘤(UM)是一种罕见疾病,在皮肤白皙、眼睛明亮的人群中发病率最高。眼睛的颜色主要由基因决定,并由一组单核苷酸多态性(SNPs)定义。我们的目的是确定是否能找出与预后有关的 SNP:设计:我们对 392 名 UM 患者外周血单核细胞中的 DNA 进行了测序,并获得了 6 个常见眼色相关 SNP 的基因型。比较了不同基因型患者的临床和组织病理学肿瘤特征、肿瘤染色体状态和患者生存率:荷兰莱顿市莱顿大学医学中心接受 UM 去核手术的 392 名患者:我们从 392 名 UM 患者的外周血白细胞中分离出 DNA,并使用 HIrisPlex-S 检测方法中的 6 个眼色 SNPs 进行测序。从测序数据中提取的基因型被上传到Hirisplex网络工具(https://hirisplex.erasmusmc.nl/),用于眼色预测。我们使用皮尔逊卡方检验(Pearson's chi-square test)和曼-惠特尼U检验(Mann-Whitney U test)检验了眼色SNP与肿瘤特征和染色体畸变的相关性,并使用卡普兰-梅耶曲线(Kaplan-Meier curves)、对数秩检验(log-rank test)和考克斯回归(Cox regression)检验了生存率:结果:在392名有可分析基因型数据的患者中,307人(78%)被指定为蓝眼睛,74人(19%)为棕色眼睛,11人(3%)不能被指定为蓝眼睛或棕色眼睛。具有蓝眼基因的患者生存率较低(p = 0.04)。这与一种基因型有关:rs12913832(HERC2)的G/G基因型编码蓝色眼睛的患者预后较差(p = 0.017),这与高危肿瘤(3号染色体单体,p = 0.04)多于A/G或A/A基因型的患者有关:rs12913832(HERC2)的G/G基因型与蓝眼睛的颜色有关,它不仅是一个与荨麻疹发病风险有关的遗传因素,而且还与较差的预后有关,因为它与高危荨麻疹(携带3号染色体单体)的发病风险较高有关。
Survival in uveal melanoma patients is linked to genetic variation at HERC2 SNP rs12913832.
Purpose: Uveal melanoma (UM) is a rare disease, with the highest incidence in people with a fair skin and light eyes. Eye colour is largely genetically determined and defined by a set of single nucleotide polymorphisms (SNPs). We set out to determine whether we could identify a SNP that is related to prognosis.
Design: We sequenced DNA from peripheral blood mononuclear cells of 392 patients with UM and obtained the genotype of six common eye colour-related SNPs. Clinical and histopathologic tumour characteristics, tumour chromosome status, and patient survival were compared among patients with different genotypes.
Subjects: 392 patients who underwent enucleation for UM at the Leiden University Medical Center, Leiden, The Netherlands.
Methods: We isolated DNA from peripheral blood leukocytes of 392 patients with UM and performed sequencing, using six eye colour SNPs from the HIrisPlex-S assay. The genotypes extracted from the sequencing data were uploaded onto the Hirisplex webtool (https://hirisplex.erasmusmc.nl/) for eye colour prediction. We tested the association of eye colour SNPs with tumour characteristics and chromosome aberrations using Pearson's chi-square test and Mann-Whitney U test and survival with Kaplan-Meier curves with log-rank test and Cox regression.
Main outcome measures: UM-related survival.
Results: Of the total cohort of 392 patients with analysable genotype data, 307 (78%) were assigned to have blue eyes, 74 (19%) brown eyes and 11 (3%) could not be assigned to either blue or brown. Patients with a genetically-blue eye colour had a worse survival (p = 0.04). This was related to one genotype: patients with the G/G genotype of rs12913832 (HERC2) which codes for blue eye colour had a worse prognosis (p = 0.017), which was related to more often having high-risk tumours (monosomy of chromosome 3, p = 0.04) than patients with an A/G or A/A genotype.
Conclusion: The G/G genotype of rs12913832 (HERC2), which is related to blue eye colour, is not only a genetic factor related to the risk to develop a UM, but is also linked to a worse prognosis, due to an association with a higher risk of developing a high-risk UM (carrying monosomy of chromosome 3).
期刊介绍:
The journal Ophthalmology, from the American Academy of Ophthalmology, contributes to society by publishing research in clinical and basic science related to vision.It upholds excellence through unbiased peer-review, fostering innovation, promoting discovery, and encouraging lifelong learning.