Soares M R, Huber J, Rios A F L, Ramos E S
Department of Gynecology and Obstetrics, School of Medicine of Ribeirão Preto, University of São Paulo, Ribeirão Preto, São Paulo, Brazil.
Growth Horm IGF Res. 2010 Aug;20(4):295-7. doi: 10.1016/j.ghir.2010.03.006. Epub 2010 May 18.
The etiology of cutaneous melanoma is complex, involving both heterogeneous genetic and environmental components. The aim of our study was to verify if single polymorphic sites within IGF2 and H19 genes and their consequent haplotypes influence risk and/or prognosis of familial melanoma.
Twenty one patients with clinical criteria of hereditary melanoma (early onset, presence of multiple primary melanoma, and/or one or more affected first- or second-degree relatives) and previously screened for CDKN2A mutations were genotyped by IGF2/ApaI and H19/RsaI PCR-RFLPs. Data were compared between patients and a control group (100 healthy young individuals) using Chi-square and Fisher's exact tests. We also investigated if these polymorphic sites could be microRNAs potential targets, using RegRNA software.
Although the IGF2 and H19 genotypes/haplotypes were not significantly associated with melanoma, two of the most severe cases (very early onset or multiple melanomas) showed to be heterozygous for both genes. We found an overlap between IGF2/ApaI and miR-615-5p, and between H19/RsaI and miR-574-3p.
Some studies have shown H19, and IGF2 genes (or related genes or protein, for example, IGF2R and IMP-3) differential expression in melanoma. However, no study has attempted to examine markers across this cluster in relation to melanoma until now. Since the base change may impair the pairing of microRNA and its binding site, our results suggest a new window for future studies of IGF2 and H19 genetic variability and posttranscriptional regulation. Due to the importance and based on the present results, we suggest that the genotype/haplotype analysis of IGF2 and H19 polymorphisms should be better investigated in large populations with cutaneous melanoma, attempting to tie the association with progression of the disease.
皮肤黑色素瘤的病因复杂，涉及多种异质性遗传和环境因素。我们研究的目的是验证胰岛素样生长因子2（IGF2）和H19基因内的单个多态性位点及其相应单倍型是否会影响家族性黑色素瘤的风险和/或预后。
对21例符合遗传性黑色素瘤临床标准（发病早、存在多发原发性黑色素瘤和/或有一个或多个一级或二级亲属患病）且先前已筛查过细胞周期蛋白依赖性激酶2A（CDKN2A）基因突变的患者，采用IGF2/ApaI和H19/RsaI聚合酶链反应-限制性片段长度多态性（PCR-RFLP）方法进行基因分型。使用卡方检验和费舍尔精确检验对患者与对照组（100名健康年轻人）的数据进行比较。我们还使用RegRNA软件研究了这些多态性位点是否可能是微小RNA的潜在靶点。
尽管IGF2和H19基因的基因型/单倍型与黑色素瘤无显著相关性，但其中两例病情最严重的病例（发病极早或有多发性黑色素瘤）显示这两个基因均为杂合子。我们发现IGF2/ApaI与微小RNA-615-5p之间以及H19/RsaI与微小RNA-574-3p之间存在重叠。
一些研究表明H19和IGF2基因（或相关基因或蛋白质，如IGF2R和IMP-3）在黑色素瘤中存在差异表达。然而，迄今为止，尚无研究尝试研究该基因簇中的标记物与黑色素瘤的关系。由于碱基变化可能会损害微小RNA与其结合位点的配对，我们的结果为未来研究IGF2和H19基因变异性及转录后调控提供了一个新的窗口。鉴于其重要性并基于目前的结果，我们建议在大量皮肤黑色素瘤患者中更好地研究IGF2和H19多态性的基因型/单倍型分析，试图将其与疾病进展联系起来。
