肾细胞癌FHIT基因蛋白编码外显子突变的研究

Alterations of the human FHIT gene in renal cell carcinoma

目的 :检测肾细胞癌 ( RCC)组织 FHIT基因 ( fragile histidine triad)蛋白编码外显子异常情况 ,了解 RCC中 FHIT基因异常特征 ,探讨 FHIT基因与 RCC发生的关系。方法 :收集 RCC及相应癌周肾组织标本 2 2份和 1 6份 ,提取组织 DNA。DIG标记 FHIT全长 c DNA探针。PCR扩增 FHIT基因 E5～ E9,产物行 Southern blot杂交。结果 :1 5份 ( 68.2 % )癌组织标本、6份( 37.5% )癌周肾组织标本存在 FHIT基因蛋白编码外显子缺失或突变 ,其中 1 0份同时存在两个外显子异常改变。癌组织及癌周肾组织 E5异常 (含缺失、异常 )发生率分别为 40 .9% ( 9/ 2 2 )和2 5.0 % ( 4 / 1 6)。结论 :FHIT基因异常可能是 RCC发生过程中的早期事件。

Purpose:To detect aberrant of FHIT gene(fragile histidine traid) exons in tissues of RCCs(renal cell carcinoma), surrounding RCCs, and normal kidney, in order to understand the feature of FHIT gene exones alteration in RCC, to inquire into the relationship between FHIT gene and development of RCC.Methods:A total of 22 RCCs and 14 surrounding tissues were obtained from surgical specimens. PCR (polymerase chain reaction) amplications of individual FHIT exons were carried out. PCR products were hybridized with DIG-labeled cDNA probes.Results:Sixty eight percent of RCCs (15/22) and 37.5% (6/16) of surrounding cancer tissues have deletion or aberrant of FHIT exons for protein, and abnormal of FHIT E5 and E8 are much more common than other exons for protein. These alterations usually involve more than one locus of FHIT exon.Conclusion:Lesions at the FHIT DNA level may be the early event in the development of RCC.