FHIT基因在食管鳞癌发生中的作用

Function of FHIT gene in carcinogenesis of squamous cell carcinoma of oesophagus

目的 研究食管鳞癌不同病变阶段脆性组氨酸三聚体（FHIT）基因mRNA水平和各主要外显子的变化，以探讨FHIT基因在食管鳞癌发生与演进中的意义。方法 采用巢式RT—PCR扩增FHIT基因全长cDNA和开放阅读框架（ORF）序列，并应用PCR扩增FHIT基因3-9外显子。结果 在食管正常组织中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或0．05）；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或0．05）；癌组织和癌前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或0．05），而且主要以ORF区外显子丢失为主。结论 FHIT基因改变（缺失）可能是食管鳞癌发生的一个重要的早期分子事件，并与食管鳞癌的发生与演进有密切关系。

Objective To investigate the changes of FHIT gene mRNA and the main exons, and analyze the function of FHIT gene in carcinogenesis of squamous cell carcinoma of oesophagus. Methods Nested RT - PCR was used to amplify the whole length cDNA and open - reading frame （ORF） of FHIT gene. The exons （3-9） of FHIT gene were amplified by PCR. Results Nested RT- PCR with the outer and inner primers amplified more abnormal fragments （included shorter fragments and no fragments） from the carcinoma tissues and precancerous tissues, compared with the normal tissues （P〈 0.01 or 〈 0.05）. Similar results were obtained by RT - PCR with the ORF primers for the amplification of FHIT ORF. FHIT gene exons （3-9） were amplified by PCR with the genomic DNA as templats and the resuits indicated that： the loss of exon in the normal tissues took place in the none - coding region while the loss of the coding region occured in the cancer tissues and precancerous tissues. It was consistent with the results of the whole length cDNA and ORF of FHIT gene by RT - PCR. Conclusion The changes of FHIT gene are probably important molecular events in carcinogenesis of squamous cell carcinoma of oesophagus, and are related to the carcinogenesis and progression.