FHIT基因在结肠癌发生中的作用

Role of FHIT gene in the development of carcinoma of colon

目的研究结肠癌不同发展阶段中脆性组氨酸三聚体基因(FHIT基因)和各主要外显子的改变情况,探讨FHIT基因在结肠癌发生中的作用。方法运用巢式RT-PCR扩增FHIT基因全长和开放阅读框架及PCR扩增FHIT基因3-9外显子。结果(1)FHIT基因全长cDNAPCR扩增结果显示:在正常组织中FHIT基因出现极低频率的异常,而在相应癌组织和癌旁组织中FHIT基因异常出现的频率显著增高(P<0.01,P<0.05);(2)FHIT基因ORFPCR扩增结果显示:正常组织中ORF无异常,而相应癌组织和癌旁组织中都出现较高频率的异常(P<0.01,P<0.05);(3)FHIT基因3-9外显子PCR扩增结果显示:癌组织和癌旁组织中出现较高频率的外显子丢失,与正常组织相比有显著性差异(P<0.01,P<0.05),而且主要以ORF区外显子丢失为主。结论FHIT基因改变可能与结肠癌的发生有关,是肿瘤发生的一个重要的早期分子事件。

Objective To investigate the changes of fragile histidine triad（FHIT ）gene and the major exon, and analyze the role of FHIT gene in the development of carcinoma of colon. Methods Nested RT-PCR was used to amplify the whole length of mRNA and open reading frame of FHIT gene , The exon 3-9 of FHIT gene was amplified by PCR. Results ＇ （ 1 ） Results of amplification of the whole length cDNA of FHIT gene by PCR demonstated： in normal tissues, low frequency of abnormality of FHIT gene occurred, while in cancinoma and adjacent tissues, there was a higher frequency in abnormality of FHIT gene（ P〈 0.01or 0.05）;（2 ）Amplification of ORF of FHIT gene by PIER shew： there was no ORF abnormality in normal tissues ,while higher frequency in ORF abnormality occurred in cancinoma and adjacent tissues （P〈0.01or 0.05）; （3）Results of FHIT gene exon 3-9 amplified by PCR indicated： Frequent loss of exon in carcinoma and adjacent tissues was significantly higher than that in normal tissues（ P 〈 0.01 or 0.05）, Loss of exon located in ORF region was predominat. Conclusion The changes of FHIT gene may play an important role and is an critical early molecular event in the process of the development of carcinoma of colon.