摘要
目的 K-ras基因在结直肠癌发生、发展中均有重要作用。K-ras野生型的患者对西妥昔单抗(Cetuximab,C225)敏感,而突变型者不敏感。文中探讨结直肠癌中K-ras基因突变情况及其临床病理学意义。方法从结直肠癌石蜡标本中提取基因组DNA,采用焦磷酸测序(pyrosequencing)法检测67例结直肠癌中K-ras基因的突变情况。结果 K-ras基因突变率为38.8%(26/67),发现6种突变类型,即第12密码子(GGT→GAT、GGT→GTT、GGT→TGT、GGT→AGT、GGT→GCT)突变和第13密码子(GGC→GAC)突变。K-ras基因突变57.7%发生在第12密码子的第2位碱基,最多见突变类型为(GGT→GAT)。女性患者K-ras基因突变率(57.7%)高于男性患者(26.8%),差异有统计学意义(P<0.05)。有淋巴结转移组K-ras基因突变率(58.8%)高于无淋巴结转移组(32.0%),差异有统计学意义(P<0.05)。K-ras基因突变与患者年龄、肿瘤位置、浸润深度、组织学类型及Dukes'分期无显著相关性(P>0.05)。结论焦磷酸测序可用于K-ras基因突变的快速检测;K-ras基因突变在女性结直肠癌患者及有淋巴结转移的患者中多见,可望成为判断结直肠癌预后的重要指标。
Objective The K-ras gene plays an important role in the development and progression of colorectal cancer. Studies show that patients with the wild type of K-ras could benefit from treatment with cetuximab （ C225 ） but those with the mutated type could not. The authors investigated the mutation of K-ras in colorectal cancer and its clinicopathological significance. Methods Genomic DNA was extracted from the paraffin-embedded tissue specimens from 67 patients with colorectal cancer. Pyrosequencing technique was used to test K-ras mutation in the patients. Results The frequency of K-ras mutation in colorectal cancer was 38.8% （26/67）. Six types of K-ras gene mutation were found, namely, codon 12 （GGT-＋GAT）, codon 12 （GGT→GTI）, codon 12 （GGT→TGT）, codon 12 （GGT→AGT）, codon 12 （GGT→GCT）, and codon 13 （GGC→GAC）. There was a 57.7% incidence of K-ras mutation at the second position in codon 12, most commonly in codon 12 （GGT→GAT） （30.8%）. The femaleshad a higher frequency of K-ras mutation than the males （57.7% vs 26.8%, P 〈 0.05 ）, and so were those with lymph node metastases than those without metastases （58.8% vs 32.0%, P 〈0.05）. K-ras mutation frequency exhibited no significant correlation age, tumor localization, invasion depth, histologic type and Dukes＇ staging （P 〉 0.05）. Conclusion The pyrosequencing technique can be used for fast detection of K-ras mutation in colorectal cancer. The frequency of K-ras mutation is more common in female colorectal cancer patients with lymph node metastases, which could be regarded as an important indicator for the prognosis of colorectal cancer.
出处
《医学研究生学报》
CAS
北大核心
2013年第1期19-22,共4页
Journal of Medical Postgraduates
基金
国家自然科学基金(30970813
81171391)
