Germline copy number variation in the YTHDC2 gene: does it have a role in finding a novel potential molecular target involved in pancreatic adenocarcinoma susceptibility?
Germline copy number variation in the YTHDC2 gene: does it have a role in finding a novel potential molecular target involved in pancreatic adenocarcinoma susceptibility?
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DOI：
10.1517/14728222.2014.920324
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发表时间：
2014-08-01
影响因子：
5.8
通讯作者：
Russo, Antonio
中科院分区：
文献类型：
--
作者：
Fanale, Daniele;Iovanna, Juan Lucio;Russo, Antonio
目的：绝大多数胰腺癌是偶发性的。生殖系基因拷贝数频繁变异的发现可以显著影响胰腺癌易感基因的表达水平。我们前瞻性地调查了散发性胰腺癌患者是否共享特定的基因拷贝数变异（CNVs）在他们的生殖系DNA.Patients和方法：DNA样本进行了分析，从72例患者的外周血白细胞诊断散发性胰腺癌和60个对照组使用Affytelium 500 K阵列集。多重连接依赖性探针扩增（MLPA）检测使用一组自行设计的MLPA探针特异性的7个目标sequence.Results：我们确定了一个包含CNV的DNA区域与胰腺癌的风险。该区域显示在72个分析的患者中的36个中缺失1个等位基因，但在对照中没有。该区域是特别感兴趣的，因为它含有编码推定的DNA/RNA解旋酶的YTHDC 2基因，这种蛋白质经常参与癌症易感性。有趣的是，82.6%的西西里病人表现出生殖细胞的一个allele.Conclusions损失：我们的研究结果表明，YTHDC 2基因可能是一个潜在的候选人胰腺癌的易感性和一个有用的标志物，早期检测以及可能的新的治疗策略的发展。
Objective: The vast majority of pancreatic cancers occurs sporadically. The discovery of frequent variations in germline gene copy number can significantly influence the expression levels of genes that predispose to pancreatic adenocarcinoma. We prospectively investigated whether patients with sporadic pancreatic adenocarcinoma share specific gene copy number variations (CNVs) in their germline DNA.Patients and methods: DNA samples were analyzed from peripheral leukocytes from 72 patients with a diagnosis of sporadic pancreatic adenocarcinoma and from 60 controls using Affymetrix 500K array set. Multiplex ligation-dependent probe amplification (MLPA) assay was performed using a set of self-designed MLPA probes specific for seven target sequences.Results: We identified a CNV-containing DNA region associated with pancreatic cancer risk. This region shows a deletion of 1 allele in 36 of the 72 analyzed patients but in none of the controls. This region is of particular interest since it contains the YTHDC2 gene encoding for a putative DNA/RNA helicase, such protein being frequently involved in cancer susceptibility. Interestingly, 82.6% of Sicilian patients showed germline loss of one allele.Conclusions: Our results suggest that the YTHDC2 gene could be a potential candidate for pancreatic cancer susceptibility and a useful marker for early detection as well as for the development of possible new therapeutic strategies.