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癌症生物學1.授課老師:生命科學系胡承波教授辦公室:基礎科學實驗館206A電話:分機2479或2480手機0920734688e-mail:cphu@thu.edu.tw2.課程目的:瞭解癌症生物學的內涵、機制、及發展。3.授課方式:a.以powerpoint講課b.提出問題，由同學發表意見及討論c.同學分組報告及討論4.對同學的期許:a.準時上課，如無法出席，須以電話(留言)、e-mail、簡訊…請假b.閱讀英文教科書c.主動參與討論，表達自己的想法及看法d.分組口頭報告(事先與老師討論)e.對同學的報告提出問題、討論及評量f.隨堂考試、期中考試、期末考試5.成績考核：由多方面考核；如準時出席、上課反應、小組參與、口頭報告、自發學習、隨堂考試、期中考及期末考6.教科書:Weinberg,R.A.TheBiologyofCancer.GarlandScience,Taylor&FrancisGroup,LLC,20077.隨時歡迎同學的口頭或書面建議TheBiologyofCancerRobertA.WeinbergGarlandScience,Taylor&FrancisGroup,LLC,2007RobertA.WeinbergWhiteheadInstituteforBiomedicalResearchMassachusettsInstituteofTechnology(MIT)RacingtotheBeginningoftheRoad:TheSearchfortheOriginofCancer–R.A.Weinberg(1996)追獵癌症：癌症病因研究之路(天下文化)OneRenegadeCell–R.A.Weinberg(1998)細胞反叛(天下文化)CuringCancer–M.Waldholz(1997)致癌基因之謎(商業週刊)Chapter1TheBiologyandGeneticsofCellsandOrganisms-1.4--1.5-Mar1,2007Figure1.11aTheBiologyofCancer(©GarlandScience2007)HumanChromosomes(duringmetaphase)pcentromereqChromosomeBanding(1970s)-Identificationofchromosomesorthechromosomerearrangementincells-Theinteractionofcertainalkylating(adding-CH3)fluorochromes(e.g.,quinacrinemustard)andhistochemicalstains(e.g.,Giemsastain)withspecificregionsofchromosomesproduces“bands”alongthechromosomesthatcanbeusedtofingerprinteachchromosomepair.Thepatternsobtaineddependonthetreatmentused.C-bandingstainscentromeres.R-bandingisthereverseofC-bandingandstainsnon-centromericregions.G-bandingisobtainedwithGiemsastain.Ityieldsaseriesoflightlyanddarklystainedbands.Q-bandingisafluorescentpatternobtainedusingquinacrineforstaining.ThepatternofbandsisverysimilartothatseeninG-banding.p:theshortarmabovethecentromere,e.g.,p13,p23q:thelongarmbelowthecentromere,e.g.,q22,q32Figure1.11bTheBiologyofCancer(©GarlandScience2007)TheDiploidKaryotypeofaNormalCell1.4ChromosomesarealteredinmosttypesofcancercellsCancercellsoftenexhibit:a.presenceofextracopiesofchromosomeb.lossofentirechromosomesc.fusionofthearmofonechromosomewithpartofanotherd.aberrantlystructuredchromosomesFigure1.11cTheBiologyofCancer(©GarlandScience2007)TheaneuploidkaryotypeofahumanbreastcancercellSidebar1.3CancercellsareoftenaneuploidEuploidy–normalconfiguration(numbers&pairs)ofchromosomesAneuploidy–changesinchromosomenumber→acquisitionofextracopiesofonechromosomeorthelossofanotherChromosomesmayundergochangesinthestructure:A-1.translocationA-2.reciprocaltranslocationPh1ThesmallerofthetworesultingabnormalchromosomesiscalledthePhiladelphiachromosome,afterthecitywheretheabnormalitywasfirstrecorded.Figure1.12dTheBiologyofCancer(©GarlandScience2007)B.deletionC.inversionM-bandfluorescenceinsituhybridization(mFISH)reveals(B)adeletionand(C)aninsertionofaportionofchromosome5Figure1.12aTheBiologyofCancer(©GarlandScience2007)HSRD.amplification1.HSR(homologouslystainingregion)2.DM(doubleminutes)-asegmentofachromosomeiscopied-asegmentiscleavedoutofamanytimesover,andtheresultingchromosome,replicateasanextracopiesmaybefusedhead-to-tailautonomous,extrachromosomalinlongarrayswithinachromosomalentity,andincreasetomanysegmentcopiespernucleus,resultingintheappearanceofsubchromosomalfragments1.5Cancer-causingmutationsoccurinboththegermlineandthesomagermcells(生殖細胞)–sperms&eggs-germlinetransmissionofmutationssoma(身體)–theanimalorplantbodyasawholewiththeexceptionofthesexcells-somaticmutationsSomecancersarehereditary,butmostarecausedbysomaticmutations.Youneedtofullyunderstandthefollowingtermshaploid,diplodkaryotypeallelehomozygous,heterozygousgenotype,phenotypedominant,recessiveincompletedominantco-dominancehaploid–describingagenomeinwhichallchromosomesarepresentinasinglecopydiploid–describingagenomeinwhichallchromosomesarepresentinpairs,oneofeachpairbeinginheritedfromafatherandtheotherfromamother,withtheexceptionofthesexchromosomes,whichinplacentalmammalsarepairedineithertheXXortheXYconfiguration.karyotype–thearrayofchromosomescarriedbyacell,asdeterminedbydetailedexaminationofthesechromosomes,usuallyperformedwithcondensedchromosomesatmetaphaseallele–onealternativeamongdifferentversionsofagenethatmaybedefinedbythephenotypethatitcreates,bytheproteinthatitspecifies,orbyitsnucleotidesequencehomozygous–referringtotheconfigurationofageneticlocusinwhichthetwocopiesofthegenecarryidenticalversions(alleles)ofthegeneheterozygous-referringtotheconfigurationofageneticlocusinwhichthetwocopiesofthegenecarrydifferentversions(alleles)ofthegenegenotype–geneticconstitutionofanorganismphenotype–ameasurableorobservabletraitofanorganismdominant–describinganalleleofagenethatdeterminesphenotypeinspiteofthepresenceofa2ndgeneallelethatspecifiesadifferentphenotyperecessive–referringtoanalleleofagenethatisunabletodictatephenotypewheninthepresenceofa2ndallelethatactsasdominantly