Detection of two novel mutations and relatively high incidence of H-RAS mutations in Vietnamese oral cancer
Detection of two novel mutations and relatively high incidence of H-RAS mutations in Vietnamese oral cancer
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DOI：
10.1016/j.oraloncology.2009.05.638
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发表时间：
2009-10-01
期刊：
影响因子：
4.8
通讯作者：
Tsuchida, Nobuo
中科院分区：
文献类型：
--
作者：
Murugan, Avaniyapuram Kannan;Hong, Nguyen Thi;Tsuchida, Nobuo
口腔鳞状细胞癌是世界上第六大常见癌症，也是越南第七大常见癌症。RAS和PI 3 K-AKT信号通路在口腔癌的发生发展中起重要作用。我们之前对PI 3 K信号通路的研究显示越南口腔癌中PIK 3CA和PTEN基因突变的缺失。因此，我们假设RAS更可能作为上游效应物被激活。然而，越南口腔癌中RAS突变的状况尚未研究。本研究对56例原发性口腔鳞癌DNA标本进行了H-RAS基因第1、2外显子热点突变的筛查，并对部分标本进行了ERK 2基因第7外显子突变的筛查。在56例肿瘤中有10例（18%）检测到H-RAS突变。发现两个新的突变，一个是在密码子10和11之间插入三个核苷酸（GGC），导致甘氨酸（10 Gly 11）的框内插入;另一个是密码子62的错义突变（GAG > GGG）。在56例肿瘤中发现12例（22%）T81 C单核苷酸多态性，ERK 2基因第7外显子无突变。H-RAS突变发生率与肿瘤的晚期和高分化肿瘤分级显著相关。我们的研究是第一个报告H-RAS突变的越南种族，有两个新的突变和相对较高的H-RAS突变的发生率。提示RAS是PI 3 K-AKT信号通路中的重要成员，在口腔癌的发生发展中可能起重要作用。(C)2009年由Elsevier Ltd.出版
Oral squamous cell carcinoma is the sixth most common cancer in the world and the seventh most common cancer in Vietnam. The RAS and PI3K-AKT signaling pathways play an important role in oral carcinogenesis. Our previous study on PI3K signaling pathway showed the absence of PIK3CA and PTEN gene mutations in Vietnamese oral cancer. We thus hypothesized that the RAS could be more likely activated as an upstream effector. However, the status of RAS mutations in Vietnamese oral cancer had not been studied. In the present study, Fifty six primary tumor DNA samples were screened for mutations of hot spots in exons 1 and 2 of H-RAS and a part of the samples for exon 7 of ERK2 gene in which we previously reported a mutation in an OSCC cell line. The H-RAS mutations were detected in 10 of 56 tumors (18%). Two novel mutations were found, one was an insertion of three nucleotides (GGC) between codons 10 and 11 resulting in in-frame insertion of glycine (10Gly11) and the other was a missense mutation in codon 62 (GAG > GGG). We also found T81C single nucleotide polymorphism in 12 of 56 tumors (22%) and there was no mutation in exon 7 of ERK2 gene. The H-RAS mutation incidence showed significant association with advanced stages of the tumor and also with well-differentiated tumor grade. Our study is the first to report H-RAS mutation from Vietnamese ethnicity, with two novel mutations and relatively high incidence of H-RAS mutations. The results suggest that RAS is an important member in the PI3K-AKT signaling and could play an important role in the tumorigenesis of oral carcinoma. (C) 2009 Published by Elsevier Ltd.