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背景与目的:食管癌3号染色体短臂(3p14)经常发生缺失或易位,脆性组氨酸三联体基因(fragilehistidinetriad,FHIT)定位于3p14.2,在许多肿瘤中均发现此基因缺失或表达异常。然而,FHIT基因在食管癌中变化的形式以及FHIT改变在食管癌发生、发展中的作用尚未明确。本研究旨在探讨FHIT基因在食管鳞癌中的变化情况及其意义。方法:用微卫星分析方法观察80例食管鳞癌中FHIT基因的缺失,并用半定量逆转录聚合酶链反应法(reversetranscriptase-polymerasechainreaction,RT-PCR)分析其中20例食管鳞癌FHITmRNA表达的变化。结果:FHIT基因内标志D3S3356、D3S3378、D3S3361在本系列的标本中为纯合子。FHIT基因旁侧微卫星位点D3S1234和D3S1540在癌旁组织具有较高的杂合度,信息个体中肿瘤组织的杂合性丢失(lossofheterozygosity,LOH)频率分别为57.69%(30/52)和67.86%(38/56)。在20例同时获得其RNA的标本中,15(75%)例出现FHIT基因的mRNA表达下调,且多发生于DNA水平伴有LOH的病例。但LOH发生与mRNA表达下调并不完全一致。结论:食管癌中FHIT基因频发异常,LOH是FHIT基因表达失调的主要机制,表观遗传学(epigenetic)变化可能与部分食管癌中FHIT基因的表达下调相关。
BACKGROUND & OBJECTIVE: The deletion or translocation of the short arm (3p14) on chromosome 3 of esophageal cancer often occurs. Fragile histidine triad gene (FHIT) is located at 3p14.2. This gene is deleted or expressed in many tumors abnormal. However, the change of FHIT gene in esophageal cancer and the role of FHIT in the occurrence and development of esophageal carcinoma have not yet been clarified. This study aimed to investigate the changes of FHIT gene in esophageal squamous cell carcinoma and its significance. Methods: FHIT gene deletion was detected in 80 cases of esophageal squamous cell carcinoma by microsatellite analysis. The expression of FHIT mRNA in 20 cases of esophageal squamous cell carcinoma was analyzed by semi-quantitative reverse transcriptase polymerase chain reaction (RT-PCR). Results: The markers D3S3356, D3S3378 and D3S3361 in FHIT gene were homozygous in this series. The frequency of loss of heterozygosity (LOH) was 57.69% (30/52) and 67.86% in the tumor tissues of individuals with D3S1234 and D3S1540, respectively. (38/56). Of the 20 specimens that simultaneously received their RNA, 15 (75%) of the specimens showed down-regulation of FHIT mRNA expression and most often occurred at DNA levels with LOH. However, the occurrence of LOH and mRNA expression is not exactly the same. CONCLUSION: FHIT gene is frequently abnormal in esophageal cancer. LOH is the main mechanism of dysregulation of FHIT gene expression. The epigenetic changes may be related to the down-regulation of FHIT gene expression in some esophageal carcinomas.