中华医学遗传学杂志
中華醫學遺傳學雜誌
중화의학유전학잡지
CHINESE JOURNAL OF MEDICAL GENETICS
2012年
2期
131-136
,共6页
谭聪%金永堂%徐鹤云%张晨烨%张虎%张伟民%陈春梅%孙肖瑜
譚聰%金永堂%徐鶴雲%張晨燁%張虎%張偉民%陳春梅%孫肖瑜
담총%금영당%서학운%장신엽%장호%장위민%진춘매%손초유
非小细胞肺癌%甲基化%RARβ基因%突变%P53基因
非小細胞肺癌%甲基化%RARβ基因%突變%P53基因
비소세포폐암%갑기화%RARβ기인%돌변%P53기인
Non-small cell lung cancer%Methylation%RARβ gene%Mutation%P53 gene
目的 研究非小细胞肺癌(non-small cell lung cancer,NSCLC)维甲酸受体β(retinoid acid receptorβ,RAR)基因甲基化与P53基因突变的关系.方法 应用甲基化特异性PCR以及PCR产物直接测序法分别检测198例原发性NSCLC组织中RARβ启动子CpG岛甲基化以及P53基因第5～9外显子的突变情况.结果 RARβ甲基化和P53突变检出率分别为58.1％和36.4％.在吸烟及男性患者中二者检出率分别高于非吸烟及女性患者；TNMⅠ期以上患者RARβ甲基化率高于Ⅰ期患者；鳞癌和腺鳞癌中P53突变率均高于腺癌(P＜0.05).RARβ甲基化的癌组织,其P53 G:C＞T:A型突变、颠换及错义突变率均高于RARβ非甲基化的癌组织(P＜0.05).P53 G:C＞T:A型而不是其他类型突变的癌组织,其RARβ甲基化率高于P53未突变的癌组织(P＜0.05)；在调整性别、年龄后该差异在整组肺癌患者(OR=3.737,95％CI:1.414～9.873)、吸烟者(OR=4.020,95％CI:1.263～12.800)、鳞癌患者(OR=5.480,95％CI:1.400～21.446)、TNM Ⅰ期以上患者(OR=3.446,95％CI:1.054～11.267)中均有统计学意义(P＜0.05).结论 非小细胞肺癌RARβ甲基化与P53 G:C＞T:A型突变有关.
目的 研究非小細胞肺癌(non-small cell lung cancer,NSCLC)維甲痠受體β(retinoid acid receptorβ,RAR)基因甲基化與P53基因突變的關繫.方法 應用甲基化特異性PCR以及PCR產物直接測序法分彆檢測198例原髮性NSCLC組織中RARβ啟動子CpG島甲基化以及P53基因第5～9外顯子的突變情況.結果 RARβ甲基化和P53突變檢齣率分彆為58.1％和36.4％.在吸煙及男性患者中二者檢齣率分彆高于非吸煙及女性患者；TNMⅠ期以上患者RARβ甲基化率高于Ⅰ期患者；鱗癌和腺鱗癌中P53突變率均高于腺癌(P＜0.05).RARβ甲基化的癌組織,其P53 G:C＞T:A型突變、顛換及錯義突變率均高于RARβ非甲基化的癌組織(P＜0.05).P53 G:C＞T:A型而不是其他類型突變的癌組織,其RARβ甲基化率高于P53未突變的癌組織(P＜0.05)；在調整性彆、年齡後該差異在整組肺癌患者(OR=3.737,95％CI:1.414～9.873)、吸煙者(OR=4.020,95％CI:1.263～12.800)、鱗癌患者(OR=5.480,95％CI:1.400～21.446)、TNM Ⅰ期以上患者(OR=3.446,95％CI:1.054～11.267)中均有統計學意義(P＜0.05).結論 非小細胞肺癌RARβ甲基化與P53 G:C＞T:A型突變有關.
목적 연구비소세포폐암(non-small cell lung cancer,NSCLC)유갑산수체β(retinoid acid receptorβ,RAR)기인갑기화여P53기인돌변적관계.방법 응용갑기화특이성PCR이급PCR산물직접측서법분별검측198례원발성NSCLC조직중RARβ계동자CpG도갑기화이급P53기인제5～9외현자적돌변정황.결과 RARβ갑기화화P53돌변검출솔분별위58.1％화36.4％.재흡연급남성환자중이자검출솔분별고우비흡연급녀성환자；TNMⅠ기이상환자RARβ갑기화솔고우Ⅰ기환자；린암화선린암중P53돌변솔균고우선암(P＜0.05).RARβ갑기화적암조직,기P53 G:C＞T:A형돌변、전환급착의돌변솔균고우RARβ비갑기화적암조직(P＜0.05).P53 G:C＞T:A형이불시기타류형돌변적암조직,기RARβ갑기화솔고우P53미돌변적암조직(P＜0.05)；재조정성별、년령후해차이재정조폐암환자(OR=3.737,95％CI:1.414～9.873)、흡연자(OR=4.020,95％CI:1.263～12.800)、린암환자(OR=5.480,95％CI:1.400～21.446)、TNM Ⅰ기이상환자(OR=3.446,95％CI:1.054～11.267)중균유통계학의의(P＜0.05).결론 비소세포폐암RARβ갑기화여P53 G:C＞T:A형돌변유관.
Objective To investigate the correlation between RARβ gene promoter methylation and P53 gene mutations in non-small cell lung cancer (NSCLC).Methods Promoter methylation of RARβ and P53 mutations of exons 5 through 9 in 198 resected primary NSCLC tissues were determined by methylation specific PCR and direct sequencing.Results RARβ gene promoter methylation and P53 mutation were detected in 58.1％ and 36.4％ of tumors,respectively.Both were higher in males than in females and in smokers than in nonsmokers.A higher prevalence of RARβ promoter methylation was found in patients with advanced stage tumors than those with TNM stage I.P53 gene mutations were more frequent in squamous cell carcinoma and adeno-squamous carcinoma than adenocarcinoma.All such differences were statistically significant (P＜0.05).Frequencies of P53 mutations,including G:C＞T:A mutations,transversions and missense mutations were significantly higher in tumors with RARβ methylation than in those without (P＜0.05).A significantly higher prevalence of RARβ methylation was found in tumors with only G:C＞T:A mutation in P53 gene than those without P53 mutations (P＜0.05).This difference (OR=3.737,95 ％CI:1.414-9.873) was still statistically significant (P＜0.05) in smokers (OR=4.020,95％ CI..1.263-12.800),squamous cell carcinomas (OR=5.480,95％CI:1.400-21.446) or patients with advanced tumors (OR=3.446,95％CI:1.054-11.267) after adjusting for age and sex.Conclusion RARβ methylation is associated with G:C＞T:A mutations in P53 gene in NSCLC.
