肿瘤防治的新挑战-肿瘤异质性, 分子分型 及个体化冶疗.ppt

肿瘤防治的新挑战

(肿瘤异质性,分子分型,及个体化冶疗)

;我国恶性肿瘤发病及死亡情况的回顾与预测;;;肿瘤防治模式;Wood,LD,et.al(Science,2007,Nov.16,Vol.318:1108)

isolatedDNAfrom11breastand11colorectaltumorsanddeterminedthesequencesbasedonexonsrepresenting20,857transcriptfrom18,191gene.Anygenethatwasmutatedinthetumorbutnotinnormaltissuefromthesamepatientswasanalyzedin24additionaltumors.

Pathwayratherthanindividualgenesappeartogovernthecourseoftumorigenesis.Disruptionofapathwaybymutationinanyoneofitsgeneticcomponentswouldpresumablyleadtosimilarchangesingrowth.The15drivermutationinanindividualtumorlikelyreflectalterationsinasimilarnumberofpathways.;Afewgene‘mountains’aremutatedinalargeproportionoftumors;mostgenesaremutatedin5%oftumorsrepresentedas‘hills’两个肿瘤突变基因重复的很少，(Science2007,318:1108);Greenman,Cetal(Nature,2007,446:153-)reported1,000somaticmutationsfoundinthecodingexonsof518proteinkinasegenesin210diversehumancancers.Therewassubstantialvariationinthenumberandpatternofmutationsinindividualcancer.Mostsomaticmutationsarelikelytobe‘passengers’thatdonotcontributetooncogenesis.However,therewasevidencefor‘driver’mutationcontributingtothedevelopmentofthecancerstudiedinapproximately120genes.;Thomas,RKetal.(Naturegenetics,2007,39:347-)determined238knownoncogenmutationacross1,000humantumorsamplesof17cancertypes.Of17oncogensanalyzed,theyfound14tobemutatedatleastonce,and298(30%)samplescarriedatleastonemutation;1).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,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

Pathwayratherthanindividualgene