食管鳞癌组织的常见基因组DNA异常改变及其临床预后的相关性分析

doi:10.3969/j.issn.1004-616x.2017.01.001

Abstract

Abstract:

OBJECTIVE: This study aimed at identifying common genomic DNA alterations in esophageal squamous cell carcinoma (ESCC) which can be used as molecular markers for the detection and prognostic determination of the disease. METHODS: Genomic DNAs were extracted from tumors and morphologically normal operative margins of 112 ESCCs. Polymerase chain reactions (PCR) and polyacrylamide gel electrophoresis (PAGE) were performed to detect alterations of six microsatellite sites on chromosomes 3p and 13q. Loss of heterozygosity (LOH) of the microsatellites was further analyzed in combination with the frequently mutated genes that had been reported in our previous study. RESULTS: Among the detected microsatellite sites,D3S1768 had the highest LOH frequency (48.9%),while D3S2452 had the lowest (28.8%). When conjointly analyzed with the frequent mutations,we discovered an optimal five-marker combination including LOH of D3S1768,D13S171,D13S1493,and mutations of TP53 and TTN. Alteration of any two markers arising together in this combination had a frequency of 75.6% which was much higher than that of any single marker. The results of survival analysis showed that there was no statistical correlation between LOH of the microsatellites in this group of ESCC and survival of the patients. However,the mutations of PBRM1 and SYNE2 mainly presented in the case of short-survival. When mutations of these two genes were combined with lymph node metastasis,the overall survival time of ESCC patients with at least two positive indicators was significantly shorter than those with only one positive index or negative ones (P=0.027). CONCLUSION: A high LOH frequency was detected with microsatellite D3S1768 in ESCC. A five-marker combination,including TP53,increased the sensitivity of detecting ESCC. PBRM1 and SYNE2 mutations combined with lymph node metastasis might become an index of ESCC prognosis.

Key words: esophageal squamous cell carcinoma, loss of heterozygosity, mutation, molecular marker, prognosis

CLC Number:

R730.7

CHANG Chen, ZHAO Xiaohan, JIANG Ye, XU Xin, CAI Yan, PEI Yuhui, ZHANG Yu, HAO Jiajie, WANG Mingrong. Identification of predominant genome DNA alterations and their clinical implication in esophageal squamous cell carcinoma[J]. Carcinogenesis, Teratogenesis & Mutagenesis, 2017, 29(1): 1-6.

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Identification of predominant genome DNA alterations and their clinical implication in esophageal squamous cell carcinoma

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