Activin Signaling in Microsatellite Stable Colon Cancers Is Disrupted by a Combination of Genetic and Epigenetic Mechanisms 英文参考文献.docVIP

下载本文档

5
0
约4.16万字
约 8页
2017-05-11 发布于上海
举报
版权申诉

Activin Signaling in Microsatellite Stable Colon Cancers Is Disrupted by a Combination of Genetic and Epigenetic Mechanisms 英文参考文献.doc

1、本文档共8页，可阅读全部内容。
2、原创力文档（book118）网站文档一经付费（服务费），不意味着购买了该文档的版权，仅供个人/单位学习、研究之用，不得用于商业用途，未经授权，严禁复制、发行、汇编、翻译或者网络传播等，侵权必究。
3、本站所有内容均由合作方或网友上传，本站不对文档的完整性、权威性及其观点立场正确性做任何保证或承诺！文档内容仅供研究参考，付费前请自行鉴别。如您付费，意味着您自己接受本站规则且自行承担风险，本站不退款、不进行额外附加服务；查看《如何避免下载的几个坑》。如果您已付费下载过本站文档，您可以点击这里二次下载。
4、如文档侵犯商业秘密、侵犯著作权、侵犯人身权等，请点击“版权申诉”（推荐），也可以打举报电话：400-050-0827(电话支持时间：9:00-18:30)。
5、该文档为VIP文档，如果想要下载，成为VIP会员后，下载免费。
6、成为VIP后，下载本文档将扣除1次下载权益。下载后，不支持退款、换文档。如有疑问请联系我们。
7、成为VIP后，您将拥有八大权益，权益包括：VIP文档下载权益、阅读免打扰、文档格式转换、高级专利检索、专属身份标志、高级客服、多端互通、版权登记。
8、VIP文档为合作方或网友上传，每下载1次，网站将根据用户上传文档的质量评分、类型等，对文档贡献者给予高额补贴、流量扶持。如果你也想贡献VIP文档。上传文档

Activin Signaling in Microsatellite Stable Colon Cancers Is Disrupted by a Combination of Genetic and Epigenetic Mechanisms 英文参考文献

ActivinSignalinginMicrosatelliteStableColonCancers IsDisruptedbyaCombinationofGeneticandEpigenetic Mechanisms BarbaraJung1,2,3*,JessicaGomez2,EddyChau1,JenniferCabral1,JeffreyK.Lee1,AimeeAnselm1, PrzemyslawSlowik1,DeenaReam-Robinson1,KarenMesser2,JudithSporn1,SungK.Shin4,C.Richard Boland4,AjayGoel4,JohnM.Carethers1,2,3 1DepartmentofMedicine,UniversityofCaliforniaSanDiego,LaJolla,California,UnitedStatesofAmerica,2MooresCancerCenter,UniversityofCaliforniaSanDiego,La Jolla,California,UnitedStatesofAmerica,3VeteransAffairsSanDiegoHealthcareSystem,SanDiego,California,UnitedStatesofAmerica,4DepartmentofMedicine, BaylorUniversityMedicalCenter,Dallas,Texas,UnitedStatesofAmerica Abstract Background: Activin receptor 2 (ACVR2) is commonly mutated in microsatellite unstable (MSI) colon cancers, leading to proteinloss,signalingdisruption,andlargertumors.Here,weexaminedactivinsignalingdisruptioninmicrosatellitestable (MSS)coloncancers. Methods:Fifty-onepopulation-basedMSScoloncancerswereassessedforACVR1,ACVR2andpSMAD2protein.Consensus mutation-prone portions of ACVR2 were sequenced in primary cancers and all exons in colon cancer cell lines. Loss of heterozygosity(LOH)wasevaluatedforACVR2andACVR1,andACVR2promotermethylationbymethylation-specificPCR andbisulfitesequencingandchromosomalinstability(CIN)phenotypeviafluorescentLOHanalysisof3duplicatemarkers. ACVR2promotermethylationandACVR2expressionwereassessedincoloncancercelllinesviaqPCRandIP-Westernblots. Re-expression of ACVR2 after demethylation with 5-aza-29-deoxycytidine (5-Aza) was determined. An additional 26 MSS colon cancers were assessed for ACVR2 loss and its mechanism, and ACVR2 loss in all tested cancers correlated with clinicopathologicalcriteria. Results:Of51MSScolontumors,7(14%)lostACVR2,2(4%)ACVR1,and5(10%)pSMAD2expression.Nosomatic ACVR2 mutations were detected. Loss of ACVR2 expression was associated with LOH at ACVR2 (p,0.001) and ACVR2 promoter hypermethylation(p,0.05).ACVR2LOH,butnotpromoterhype