FGFR4基因单核苷酸多态性和杂合性丢失在胃癌发病中的作用

Roles of single nucleotide polymorphism and loss of heterozygosity of FGFR4 gene in oncogenesis of gastric carcinoma

目的研究成纤维细胞生长因子受体4(FGFR4)基因在胃癌患者中的单核苷酸多态性(SNP)情况和杂合性丢失(LOH)的发生频率,探讨其在肿瘤发生发展和患者预后判断中的意义。方法检测50例胃癌标本中FGFR4基因5个外显子区域6、9、13、16、18的SNP情况,并以SNP技术检测FGFR4基因外显子9区域内密码子388位点rs351855的LOH,分析FGFR4基因SNP和LOH与胃癌临床病理特征及患者生存率的关系。结果 FGFR4基因的外显子9区域第401密码子发生1例体细胞突变(R401C,C>T),34例胃癌发生编码区非同义SNP,GG、AG、AA三种基因型比例分别为32%、52%和16%。26例AG型杂合子胃癌患者中,rs351855位置LOH的发生频率为92.31%。LOH发生频率和Arg388等位基因的表达在不同肿瘤分化程度、浸润深度、淋巴结转移、pTNM分期及患者生存率中的差异均无统计学意义(P>0.05)。结论胃癌患者FGFR4第388密码子rs351855位点发生高频LOH,提示在其附近存在抑癌基因的缺失或失活。Arg388等位基因的表达和FGFR4基因rs351855位点LOH不直接影响胃癌的发展及患者的预后。

Objective To investigate the single nucleotide polymorphism （SNP） and loss of heterozygosity （LOH） of fibroblast growth factor receptor 4 （FGFR4） gene in gastric carcinoma, and explore their roles in oncogenesis, progression and prognosis of gastric carcinoma. Methods The SNP of FGFR4 gene exon 6, 9, 13, 16 and 18 of 50 cases of gastric carcinoma was detected. The LOH of rs351855 of coden 388 in FGFR4 gene exon 9 was determined by SNP technique. The correlation of SNP and LOH of FGFR4 gene with clinicopathology of gastric carcinoma and survival of patients was analysed. Results There was somatic mutation of coden 401 （R401C,C〉T） in FGFR4 gene exon 9 in 1 case, non-synonymous SNP was detected in 34 cases of gastric carcinoma with the percentages of GG genotype, AG genotype and AA genotype being 32%, 52% and 16% respectively, and the frequency of LOH of rs351855 was 92.31% in 26 case of gastric carcinoma with AG genotype. There was no significant difference in the expression of Arg388 allele and frequency of LOH among different degrees of differentiation, tumor stages, lymph node status, pTNM classification and time of survival （P〉0.05）. Conclusion High frequency of LOH of rs351855 of coden 388 in FGFR4 gene in patients with gastric carcinoma suggests that there is absence or inactivation of tumor suppressor gene nearby. The expression of Arg388 allele and LOH of rs351855 in FGFR4 gene are not associated with the progression and prognosis of gastric carcinoma.