中国人散发性大肠癌APC基因突变的研究

APC mutation in sporadic colorectal cancer in China

目的观察中国人大肠癌APC基因突变情况,并结合临床病理资料加以分析.方法应用常规酚、氯仿法提取48例散发性大肠癌组织及相应正常黏膜组织的DNA,聚合酶链反应(PCR)扩增、单链构象多态性(SSCP)电泳和DNA直接测序,检测APC基因第15外显子MCR区段的突变情况.结果 APC基因突变率为37.5%(18/48),APC基因第15外显子MCR区段突变发生在codon1306～codon1442之间,突变类型有点突变(A→G、G→T、C→A、C→T、G→A)、移码突变(-A、-C、-G、-AG、+T、+A、+AACG).结论中国人大肠癌APC基因突变率为37.5%(18/48),以体细胞的错义突变为主,codon1309∽codon1356是大肠癌APC基因突变热区,而codon1356(CCT→TCT)是突变热点.散发性大肠癌APC基因突变与患者的年龄、性别、肿瘤的位置、浸润深度、组织类型、分化程度、远处转移、Dukes'分期和5年生存无关.

Objective To detect APC mutation in sporadic colorectal cancer in China and its correlation with parameters of clinical pathology. Methods DNA from 48 patients with sporadic colorectal cancer was extracted by standard phenol/chloroform method. APC gene was amplified by using polymerase chain reaction （PCR） and analyzed by single strand conformation polymorphisms （SSCP） and DNA direct sequencing. Mutations in mutation cluster region （MCR） of exon15 were analyzed. Results Mutations of APC gene lay from codon1306 to codon1442. The types of mutation included point mutation and transfer mutation. The point mutations included： A→G, G→T, C→ A, C→T and G→A, and the transfer mutations included ： -A, -C, -G, ＋ A and ＋ AACG. Conclusion The frequency of APC gene mutation in sporadic colorectal cancer was 37.5 % （18/48） in China. The missence of somatic mutations occupied the most among all mutations of colorectal cancer. Codon 1309-codon 1356 were the mutation cluster region of exon15 and codon1356 （CCT→TCT） was the hot point mutation. The frequency of APC mutation is not correlated with the parameters of clinical pathology except lymph metastasis.