????????????( clonal proliferation)

1
??? ???????

• ????????????( clonal proliferation)
• ??????????????????
• ?????????????????
• ???????,??????????????,??????????
• ?????????????????????

2
(No Transcript)
3

• ???????
• ??????(cycIin)?????????????? (cyclin-dependent
  kinase, CDK)????
• ???????????? CDKs?cyclins ???????
• CDK?????cyclin-CDK???(CKIs)???????????

4

• ??????

5

• ????(oncogene)
• 1911?Rous????????????????,??????
• ???????????????????(v-onc)
• ????????,????????? (e-onc)
• ???????????????????
• ? ???,???????????,?????????????????(?)???(
  proto-oncogene)

6

• ?(?)???
• ?????????????????????
• ????
• ?????sis????????????-?????????????
• ??????????
• ??????????( epidermal growth factor receptor,
  EGFR)
• ??????1??(CSF1R)????, CSF1R?? ?????????????????

7

• ?????????( Intracellular signal transduction
  systems)
• RAS?????????G-protein???,???????Gprotein?????????
  ?
• ???-?????( protein tyrosine kinase)
  ABL????????????????????
• ??????
• MYC?DNA????,?JUN?????
• ?????????
• ?????????????????,

8
(No Transcript)
9

• ??????
• ?????????????????
• HIV ???????????????????,??????????????????????????
  ????
• ??????????????
• ???????????????????
• ??????????????,????????????????? ?
• ????????????????????,?????????

10
(No Transcript)
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(No Transcript)
12

• ??????( tumor suppressor gene)
• ?????,??????????????( dominant effect)
• ???oncogene?????,?tumor suppressor gene
• ???????????? ??????????????
• ??????????? ( recessive)
• RB??
• ???????( retinoblastoma, RB) ,????????????
• ????????????,?????????
• ?1/3?RB?????????,?????????,????????????????,??????
  ?

13

• RB?????
• ?????pRb?????????
• pRb ?????????????
• pRb???GI??????????????,???pRb????????????,??RB????
  
• ?????( G0IG I) , pRb?????
• Gl???,????????????
• ?????pRb???S??????????????????

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(No Transcript)
15

• p53??
• ?????????,?????17p , p53?????(53 kD)
• ?????????70??? p53??
• 50????40?????p53??????
• ???????????p53?????????
• ????????????
• ??alleles?????
• ??allele????????, ????????????????

16

• ?????, p53?????
• DNA???, p53?????,??
• ??????????( apoptosis)
• p53???p21?????????
• p21??????CDK ?????
• ???CDK2?CDK4?CDK6,????????
• ??? ?S???,????????DNA
• ???????S?,?????????DNA,?p53??????
• ??????????????,p53????????( guardian of genome)

17

• ????(apoptosis, programmed cell death)?????
• ????????????????????, Apoptosis???????
  ?,?????????????
• ????????????????????,????????
• ???????
• ?????????????????,?????????????? ?,????????????

18

• ????????
• ?????????????,??????????
• ??????????????????????
• ??DNA???????????,????????
• ???????????,??????????????????,?????????

19

• ?????????????????
• ???????15????????
• ced-3?ced-4????
• ced-9?????ced-3?ced-4????? ???????
• ???????
• ced-3 vs ?????????( cysteine proteases) caspases
• ced-9 vs Bcl-2????
• ced-4 vs Apaf-l (HeLa??)

20

• caspase?????,???????????? ??????
• caspase???????????????
• ?????????, caspase ?????????caspase?????
• ???caspases????????????
• ?????????actin?Gas2?Lamins
• ??DNA???PARP?DNA-PK
• ??????PKC-d?PITSLRE kinase
• ????14???????caspases?????

21

• ??caspases???? ?????????????,???
• Initiator (upstream) caspases
• Effector (downstream) caspases
• ????????,??initiator caspases (???8?9?10 )???
• ??effector caspases???
• ???caspases-3?6?7,???????????????
• ??cytochrome c ?Apaf-l?caspase-9???apoptosome???
• ??caspase-9??caspase????

22

• ???????????????,????????? ????????
• ????????????????AIDS ??????????
• ????( proto- oncogene)???????????apoptosis???
• MYC?????????????????
• MYC?MAX??????????????????,????????????
• ????????,?p53?APC?PTEN??????? ?????????,?????????
  ???????????

23
(No Transcript)
24

• ???????
• ???????
• ????????????????
• ??????,???????????(??? ???????????)
• ????????????????,???????????????
• ??FISH?????????????
• ????FISH (multifluor-FISH)
• DNA?????
• ??????
• ?????

25
(No Transcript)
26
(No Transcript)
27

• ??????????????????????,?????
• ???????????
• ????????????
• ????
• ???????
• ???????????(????, angiogenesis)
• ????????????

28
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29

• ??????MSI
• ????STR???,??STR??????????,??????pattern
• Microsatellite DNA markers???????????????????
• Mao et al. (1996) ,??microsatellite
  analysis??????????,?95????
• DNA???????( loss of heterozygosity?LOH)
• ?????????-???DNA,???????(? SNP?STR?VNTR)
  ,?????????????,???????
• ???????????????,????????????

30
(No Transcript)
31

• DNA??????
• ????????????CpG islands
• ??????????????????
• ???????, DNA????????????????????
• ????????????CpG??????,?????????????

32
(No Transcript)
33

• ?????
• ?????????(Laser capture microdissection,LCM)
• ??????????????????????(????? ???????????)
• ??????????????????? ??
• ????????????????????????????? ???
• LCM??????????????????????????????????

34

• 1996????NIH Liotta??????
• ????????ethylene-vinyl acetate (EVA)?
• ????????????
• ??????????,?????,??
• ????????????
• ??LOH (Loss of heterozygosity )
• ???????????????????????
• ?????????????????
• p53?APC?????LOH
• ???????CE??

35
(No Transcript)
36

• ??MSI (microstatellite instability )
• ?????????( replication error) ,???????????????
• ?????????????????????? DNA???
• MSI?DNA??????????
• DNA????????, LOH?promoter????,???????????????)

37
(No Transcript)
38

• ???????(protein truncation test, PTT )
• ???????????
• ???????????????
• ???????
• ??????stop codon??????
• ?????( frameshift mutation)
• ??????????????????
• ??????????????(????????????)????????

39
(No Transcript)
40
(No Transcript)
41
(No Transcript)
42

• ??????
• ??????????????? ?????????Ig?T?????????
• ????????????????????
• ???????????????????( 1987???????)
• V?????5??????J???????? 3 ???
• ??????????????V-D?D-J??????????,??PCR?????????????
  ??(smeared)
• B?? ??????????????,????VDJ????,???????????

43

• ??????????
• ??p53?????17??????13?1?(17p13.1)?
• ??? 20 kb ?11?exon?10?intron??,??393???
• 90?????????????????58 exon?
• ??????????273? 175?248?245?249?282????
• ?p53??????, Affymetrix?? ?p53??exon
  58??????????????,????p53 GeneChip

44

• ?????????????? (??)?????
• ????????????????,???????????
• ??????????????,??????????

45

• ???????( minimal residual disease, MRD)
• ??????????,??????????
• ??? FISH???,????????????
• ?????????PCR?????????????????? ???????
• ?????????,????????????
• ????????????????????,???real-time RTPCR?nested
  RT-PCR?????????????????

46

• ?????????
• ????????????
• ?????????????
• ????? PCR,??????????????????
• ?????,???????????, non-coding RNA (?micro RNA)
  ???
• ??RT-PCR?real-time qRFPCR, micro RNA array, exon
  array????????