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Epigenetic alterations in preneoplastic and neoplastic lesions of the cervix.doc

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Epigenetic alterations in preneoplastic and neoplastic lesions of the cervix

Saavedraetal.ClinicalEpigenetics2012,4:13 /content/4/1/13 REVIEW OpenAccess Epigeneticalterationsinpreneoplastic andneoplasticlesionsofthecervix KathleenSaavedra1,PriscillaBrebi1andJuanCarlosRoa1,2,3* Abstract Cervicalcancer(CC)isoneofthemostmalignanttumorsandthesecondorthirdmostcommontypeofcancerin womenworldwide.Theassociationbetweenhumanpapillomavirus(HPV)andCCiswidelyknownandaccepted (99.7%ofcases).Atpresent,thepathogenesismechanismsofCCarenotentirelyclear.Ithasbeenshownthat inactivationoftumorsuppressorgenesandactivationofoncogenesplayasignificantroleincarcinogenesis,caused bythegeneticandepigeneticalterations.Inthepast,itwasgenerallythoughtthatgeneticmutationwasakey eventoftumorpathogenesis,especiallysomaticmutationoftumorsuppressorgenes.Withdeeperunderstanding oftumorsinrecentyears,increasingevidencehasshownthatepigeneticsilencingofthosegenes,asaresultof aberranthypermethylationofCpGislandsinpromotersandhistonemodification,isessentialtocarcinogenesisand metastasis.Thetermepigeneticsreferstoheritablechangesingeneexpressioncausedbyregulationmechanisms, otherthanchangesinDNAsequence.SpecificepigeneticprocessesincludeDNAmethylation,chromotin remodeling,histonemodification,andmicroRNAregulations.Thesealterations,incombinationorindividually,make itpossibletoestablishthemethylationprofiles,histonemodificationmaps,andexpressionprofilescharacteristicof thispathology,whichbecomeusefultoolsforscreening,earlydetection,orprognosticmarkersincervicalcancer. ThispaperreviewsrecentepigeneticsresearchprogressintheCCstudy,andtriestodepicttherelationships betweenCCandDNAmethylation,histonemodification,aswellasmicroRNAregulations. Keywords:Cervicalcancer,Humanpapillomavirus,Epigeneticsalterations,Biomarkers Review Cervical cancer precursory lesions that evolve slowly and progressively, which can then advance to slight, moderate, and severe Cervical cancer (CC) is the second most prevalent neo- stages of dysplasia. CC may evolve into cancer in situ, plasia in women worldwide and