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1、肿瘤防治的新挑战(肿瘤异质性,分子分型,及个体化冶疗)中国医学科学院北京协和医学院肿瘤研究所肿瘤医院程书钧我国恶性肿瘤发病及死亡情况的回顾与预测预计在2020年，全球新发病例将达1500万(我国占1/5)，死亡1000万(我国占1/4)，现患病例3000万。肿瘤防治模式高危个体癌前病变占位病变预防予警、发现手术、放疗、化疗生物，初级阶段Wood,LD,et.al(Science,2007,Nov.16,Vol.318:1108)isolatedDNAfrom11breastand11colorectaltumorsanddeterminedthesequ
2、encesbasedonexonsrepresenting20,857transcriptfrom18,191gene.Anygenethatwasmutatedinthetumorbutnotinnormaltissuefromthesamepatientswasanalyzedin24additionaltumors.Pathwayratherthanindividualgenesappeartogovernthecourseoftumorigenesis.Disruptionofapathwaybymutationinanyoneofitsgene
3、ticcomponentswouldpresumablyleadtosimilarchangesingrowth.The<15drivermutationinanindividualtumorlikelyreflectalterationsinasimilarnumberofpathways.Afewgene‘mountains’aremutatedinalargeproportionoftumors;mostgenesaremutatedin<5%oftumorsrepresentedas‘hills’两个肿瘤突变基因重复的很少，(Science200
4、7,318:1108)Greenman,Cetal(Nature,2007,446:153-)reported1,000somaticmutationsfoundinthecodingexonsof518proteinkinasegenesin210diversehumancancers.Therewassubstantialvariationinthenumberandpatternofmutationsinindividualcancer.Mostsomaticmutationsarelikelytobe‘passengers’thatdonotco
5、ntributetooncogenesis.However,therewasevidencefor‘driver’mutationcontributingtothedevelopmentofthecancerstudiedinapproximately120genes.Thomas,RKetal.(Naturegenetics,2007,39:347-)determined238knownoncogenmutationacross1,000humantumorsamplesof17cancertypes.Of17oncogensanalyzed,they
6、found14tobemutatedatleastonce,and298(30%)samplescarriedatleastonemutation1).Wood,LD,et.aldeterminedthe乳腺癌和结直肠癌DNAsequencesbasedonexonsof20,857transcriptfrom18,191gene.(Science,2007,Nov.16,Vol.318:1108)2).ThomasRK,etal分析17类肿瘤238个oncogenes的突变(Naturegenetics,2007:39;153-)3).Greenman
7、,C;etal.分析210个不同人的肿瘤的518proteinkinasegeneexons的突变(Nature,2007,446::153-)两个肿瘤之间突变基因重复的很少Pathwayratherthanindividualgenesappeartogovernthecourseoftumorigenesis.Disruptionofapathwaybymutationinanyoneofitsgeneticcomponentswouldpresumablyleadtosimilarchangesingrowth.Thedifferencesarel
8、ikelytobethebasisforthewidevariationintu
