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首页> 外文期刊>Comparative and functional genomics >Methylation Analysis of Several Tumour Suppressor Genes Shows aLow Frequency of Methylation ofCDKN2AandRARBin Uveal Melanomas
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Methylation Analysis of Several Tumour Suppressor Genes Shows aLow Frequency of Methylation ofCDKN2AandRARBin Uveal Melanomas

机译：几个肿瘤抑制基因的甲基化分析显示葡萄膜黑素瘤中CDKN2A和RARB的甲基化频率较低

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We have investigated the frequency of methylation of several tumour suppressor genes in uveal melanoma. As the loss of one copy of chromosome 3 (monosomy 3),which is found in about half of these tumours, is tightly associated with metastaticdisease, a special emphasis was laid on genes located on this chromosome, includingthe fragile histidine triad (FHIT), von Hippel–Lindau (VHL), β-catenin (CTNNB1),activated leukocyte cell adhesion molecule (ALCAM) and retinoic acid receptor-β2(RARB) genes. In addition, the methylation patterns of the CpG-rich regions 5′of the E-cadherin (CDH1), p16/cyclin-dependent kinase inhibitor 2 A (CDKN2A)and retinoblastoma (RB1) genes were analysed by bisulphite genomic sequencing ormethylation-specific PCR (MSP). Furthermore, the SNRPN andD15S63loci, whichare located in the imprinted region of chromosome 15, were included in the study.Aberrant methylation was detected in nine of 40 tumours analysed: The imprintedSNRPNandD15S63loci were hypermethylated in three tumours, all of which retainedboth copies of chromosome 3. MethylatedRARBalleles were detected in threetumours, whereas in three other tumoursCDKN2Awas found to be methylated.As we did not find RARB and CDKN2A preferentially methylated in tumours withmonosomy 3, which is a significant predictor of metastatic disease, we suggest thatthese genes may play a causative role in the formation of uveal melanoma but not inthe development of metastases.
机译：我们调查了葡萄膜黑色素瘤中几个肿瘤抑制基因的甲基化频率。由于在这些肿瘤的大约一半中发现了一个3号染色体的丢失（单体3），它与转移性疾病密切相关，因此特别强调了位于该染色体上的基因，包括易碎的组氨酸三联体（FHIT）， von Hippel–Lindau（VHL），β-catenin（CTNNB1），活化的白细胞粘附分子（ALCAM）和视黄酸受体-β2（RARB）基因。此外，通过亚硫酸氢盐基因组测序或甲基化特异性分析了E-钙粘蛋白（CDH1），p16 /细胞周期蛋白依赖性激酶抑制剂2 A（CDKN2A）和成视网膜细胞瘤（RB1）基因的富含CpG区域5'的甲基化模式。 PCR（MSP）。此外，研究还包括位于15号染色体印迹区域的SNRPN和D15S63loci在分析的40个肿瘤中有9个检测到异常甲基化：印迹的SNRPN和D15S63loci在三个肿瘤中都被高度甲基化，所有这些都保留了3号染色体的两个拷贝。在三个肿瘤中检测到甲基化的RARB等位基因，而在其他三个肿瘤中发现了CDKN2A被甲基化。由于我们没有发现RA 3和CDKN2A在具有3号单体性的肿瘤中优先甲基化，这是转移性疾病的重要预测因子，因此我们建议这些基因可能在导致肿瘤转移的原因中起着重要作用。葡萄膜黑色素瘤的形成，而不是转移的发展。

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