胰腺导管腺癌患者KRAS与SMAD4基因的突变情况

KRAS and SMAD4 gene mutations in patients with pancreatic ductal adenocarcinoma

目的:研究胰腺导管腺癌(pancreatic ductal adenocarcinoma,PDAC)患者KRAS与SMAD4(也称DPC4)基因的突变情况,并探讨两者与PDAC患者临床病理特征的相关性。方法:收集50例未经放化疗的PDAC患者的肿瘤石蜡标本,通过Sanger测序法检测KRAS基因2号外显子与SMAD4基因全外显子的突变情况,并分析突变与临床病理特征之间的关系。结果:KRAS基因2号外显子突变率为72%(36/50),其中35例患者发生第12密码子错义突变(p.Gly12A sp 23例,p.Gly12Arg 2例,p.Gly12Val 8例,p.Gly12Cys 2例),1例患者同时发生第6密码子错义突变c.16C>T[p.(Leu6Phe)]和第23密码子同义突变(c.67C>T)。KRAS基因突变与肿瘤分期(P<0.01)、分化程度低(P<0.05)及淋巴结转移(P<0.01)相关。未检测出SMAD4外显子有突变。结论:KRAS基因与山东地区PDAC患者恶性程度高、预后差相关。SMAD4突变在本地区PDAC患者中较为罕见,提示SMAD4突变存在地区差异性。

Objective： To investigate the mutations of KRAS and SMAD4 （DPC4） genes and to determine the relationship between the gene mutations and clinicopathological characteristics in patients with pancreatic ductal adenocarcinoma （PDAC） in Shandong Province. Methods： Fifty paraffin-embedded tissues from patients with PDAC without radiotherapy and chemotherapy were enrolled in this study. The KRAS gene exon 2 and the whole exons of SMAD4 gene were sequenced by Sanger sequencing. The relationship between mutations and clinicopathological features was analyzed. Results： The mutation rate of KRAS gene exon 2 was 72% （36/50）, including 35 cases with mutations at codon 12 （p.Gly12Asp 23 cases, p.Gly12Arg 2 cases, p.Gly12Val 8 cases, p.Gly12Cys 2 cases）, and 1 case with mutations at codon 6 c.16C〉T [p.（Leu6Phe）] and codon 23 （c.67C〉T）. The KRAS mutations were associated with tumor stage （P〈0.01）, poor differentiation （P〈0.05） and lymph node metastasis （P〈0.01）. No mutation in the whole exons of SMAD4 gene was detected in this study. Conclusion： The mutation of KRAS gene is significantly associated with malignancy and poor prognosis in patients with PDAC in Shandong Province. SMAD4 mutation is rarely detected in these patients, which indicates possible geographic discrepancy of SMAD4 gene mutation.