[食管鳞状细胞癌中FHIT基因表达的等位基因缺失与下调]

[Allelic loss and down-regulation of FHIT gene expression in esophageal squamous cell carcinoma].

作者信息

Liu Fu-Xing, Huang Xiao-Ping, Zhao Chun-Xia, Xu Xin, Han Ya-Ling, Cai Yan, Wu Ren-Liang, Wu Min, Zhan Qi-Min, Wang Ming-Rong

机构信息

National key Laboratory of Molecular Oncology, Cancer Institute (Hospital), Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100021, PR China.

出版信息

Ai Zheng. 2004 Sep;23(9):992-8.

DOI:

PMID:15363189

Abstract

BACKGROUND & OBJECTIVE: Deletions and translocations involving the short arm of chromosome 3 (3p14) have been observed frequently in esophageal cancer. Fragile histidine triad (FHIT) gene is located in 3p14.2, and its deletion or abnormal expression was found in many kinds of cancers. The study was to investigate the alterations of FHIT gene, and its significance in esophageal squamous cell carcinoma (ESCC).

METHODS

The deletion of FHIT gene in 80 cases of ESCC was evaluated by microsatellite analysis, and the mRNA expression of FHIT gene in 20 cases of ESCC was analyzed by reverse transcriptase-polymerase chain reaction (RT-PCR).

RESULTS

Intragenic markers of FHIT gene, D3S3356, D3S3378, and D3S3361, showed homozygous in all samples. D3S1234 and D3S1540, located near FHIT, presented high heterozygosity. In the tested informative cases, loss of heterozygosity (LOH) of D3S1234 was detected in 30 out of 52 tumors (57.69%), and that of D3S1540 was observed in 38 out of 56 carcinomas (67.86%). Reduced expression of FHIT mRNA occurred in 15 of 20 (75.00%) cases, and was often accompanied with LOH. However, the FHIT down-regulation was not always coincident with LOH.

CONCLUSIONS

The abnormal expression of FHIT gene occurred frequently in ESCC. LOH was the main factor leading to down-regulation of FHIT expression. Epigenetic mechanism might be associated with reduced expression of FHIT in a part of ESCC cases.

摘要

背景与目的

在食管癌中经常观察到涉及3号染色体短臂（3p14）的缺失和易位。脆性组氨酸三联体（FHIT）基因位于3p14.2，在多种癌症中发现其缺失或异常表达。本研究旨在探讨FHIT基因在食管鳞状细胞癌（ESCC）中的改变及其意义。

方法

采用微卫星分析评估80例ESCC中FHIT基因的缺失情况，采用逆转录聚合酶链反应（RT-PCR）分析20例ESCC中FHIT基因的mRNA表达。

结果

FHIT基因的基因内标记D3S3356、D3S3378和D3S3361在所有样本中均显示纯合。位于FHIT附近的D3S1234和D3S1540呈现高杂合性。在检测的信息性病例中，52个肿瘤中有30个（57.69%）检测到D3S1234的杂合性缺失（LOH），56个癌中有38个（67.86%）观察到D3S1540的杂合性缺失。20例中有15例（75.00%）出现FHIT mRNA表达降低，且常伴有LOH。然而，FHIT下调并不总是与LOH一致。