MGMT基因甲基化状态在结直肠锯齿状病变中的表达及意义［摘耍］目的观察锯齿状病变组织中MGMT基因甲基化状态和MGMT蛋白表达，探讨临床病理意义和在癌变通路中的作用，同时探讨MGMT基因在不同年龄层段甲皋化状况。方法应用Taqman探针qPCRCMelhyLight)方法检测北京军区总医院2007-2013年的225例锯齿状病变［包括96例增生性息肉(HP)、61例广基(无蒂)锯齿状腺瘤/息肉(SSA/P)和68例传统型锯齿状腺瘤(TSA)］、54例管状腺瘤(TA)、69例结直肠癌(CRC)和42例正常结直肠黏膜组织中MGMT基因CpG岛甲基化状态，并通过测序法验证扩增的目的片段甲基化状态，同时应用免疫组化方法检测其中116例锯齿状病变(包括52例HP、41例SSA/P、23例TSA)、20例TA、24例CRC和24例正常结直肠黏膜组织中MGMT蛋白的表达情况。结果MGMT基因启动子甲基化状态和MGMT蛋白异常阳性程度在锯齿状病变和对照组中差异均有统计学意义(P0.05)o结论组织中MGMT基因甲基化可能诱导其蛋口表达下调的」-要原W,在结直肠“增生性息肉-锯齿状腺瘤-癌”的锯齿状癌变通路中起重耍作用。［关键词］DNA甲基化；MGMT基因；qPCR；DNA探针；锯齿状病变［］R735.3［文献标识码］A［］1673-7210(2014)01(b)-0011-06ExpressionandsignificanceofMGMTgenemethylationstatusincolorectalserratedlesionsXUChunweiWANGLupingAGEChangDepartmentofPathology,theMilitaryGeneralHospitalofBei激ngPLA,Bei激ng100700,China[Abstract]ObjectiveTodiscusspatientswithserratedlesionstissuesMGMTgenemethylationstatusandMGMTproteinexpressionandcancerpathwaysandtheroleandclinicalsignificanceofMGMTgeneindifferentageparagraphmethylationlevel・MethodsFrom2007to2013intheMilitaryGeneralHospitaiofBei激ng卩LA,225casesofserratedlesions[96casesofhyperplasticpolyp(HP),61casesofsessileserratedadenoma/polyp(SSA/P)and68casesoftraditionalserratedadenoma(TSA)],54casesoftubularadenoma(TA),69casesofcolorectalcancer(CRC)and42casesofnormalcolorectaJmucosatissueswereselected；MGMTgenemethylationstatusofCpGislandwasdetectedbyqPCRapplicationsTaqmanprobe(MelhyLight)methods,methylationstaleofamplificationtargetfragmentwasverifiedbybysequencingmethod,atthesametime,MGMTproteinexpressionin116casesofserratedlesions(including52casesofHP,41casesofSSA/P,23casesofTSA),20casesofTA,24casesofCRC,24casesofnormalcolorectalmucosatissuewasdetectedbyimmunohistochemicalmethod・ResultsThedifferencesofMGMTgenepromotermethylationstateanddegreeofabnormalMGMTproteinpositivedegreeintheserratedlesionsandthecontrolgroupwerestatisticallysignificant(P0.05)・ConclusionOrganizationMGMTgenemethylationmayinducetheproteinexpressioninthemainreasonforthedowngrade,itplaysaniinportantroleinserratedcancerationpathwayofhyperplasticpolyps-serratedadenoma-carcinonia.［Keywords］DNAmethylation；MGMTgene；qPCR；DNAprobe；Serratedlesions锯齿状病变是一组具有锯齿状(波浪状或星状)结构的异质性上皮病变，包括增生性息肉(hyperplasticpolyp,HP)、广基(无蒂)锯齿状腺瘤/息肉(sessileserratedadenoma/polyp,SSA/P)>传统型锯齿状腺瘤(traditionalserratedadenoma,TSA)O新近统计发现,结直肠癌(colorectalcancer,CRC)中60%的来自普通腺瘤,35%来自“增生性息肉-锯齿状腺瘤-癌”这条锯齿状通路［1］,特别是锯齿状病变的CpG岛甲基化表型(CpGislandmethylatorphenotyp,CTMP)O锯齿状通路涉及一系列异常的表观遗传学修饰［2］。这些异常修饰中以DMA甲基化最常见。DNA异常甲基化分为A型和C型，前者与年龄因素有关，年龄越大，甲基化频率越高，后者与肿瘤相关，通过引起相关基因表达下调或沉默，促进肿瘤的发生发展［3］。MGMT为DNA损伤修复基因,定位于人类染色体10q26,全长170kb,由5个外显子，4个内含子组成。启动子富含GC碱基，顺式作用元件有CpG岛中的6个Spl位点、2个糖皮质激索反应元件(GRE),AP-I元件等。cDNA长约7...