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Have a positive role in cell division Have a negative role in cell division Have a role in the maintenance of DNA integrity Genes altered in cancer typically:

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Presentation on theme: "Have a positive role in cell division Have a negative role in cell division Have a role in the maintenance of DNA integrity Genes altered in cancer typically:"— Presentation transcript:

1 Have a positive role in cell division Have a negative role in cell division Have a role in the maintenance of DNA integrity Genes altered in cancer typically:

2 Tumor Suppressor Genes Not enough of a good thing….

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4 1 / 10 6 1 / 10 6 = 10 12

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10 Inactivation of a Tumor Suppressor Gene Change the function of a gene product

11 Inactivating mutation Point mutation Insertion Deletion Frameshift

12 “Second Hit” = 2 nd copy inactivation 1 / 10 6 1 / 10 12

13 Loss of Heterozygosity: Heterozygote becomes homozygous by some mechanism Loss of an allele (i.e., hemizygosity)

14 “Second Hit” = 2 nd copy inactivation LOH by MITOTIC RECOMBINATION 1 / 10 4 – 1 / 10 5

15 “Second Hit” = 2 nd copy inactivation LOH by GENE CONVERSION

16 “Second Hit” = 2 nd copy inactivation LOH by NONDISJUNCTION

17 hemizygosity “Second Hit” = 2 nd copy inactivation LOH by NONDISJUNCTION

18 “Second Hit” not required due to HAPLOINSUFFICIENCY

19 Mutation within the coding region “Second Hit” o Mitotic recombination o Gene conversion o Non-disjunction Haploinsufficiency Decrease protein activity by:

20 Inactivation of a Tumor Suppressor Gene Change gene Expression

21 N C N C N C No TF SP-1 AP-2 Decrease promoter utilization by POINT MUTATION

22 Decrease promoter utilization by HYPER-METHYLATION

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24 NormalAdenocarcinomaAdvanced Colon Carcinoma

25 Decrease promoter utilization by HYPERMETHYLATION

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27 Decrease protein production by: : Mutation within the promoter region “Second Hit” o Mitotic recombination o Gene conversion o Non-disjunction Haploinsufficiency Hypermethylation

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32 Have a positive role in cell division Have a negative role in cell division Have a role in the maintenance of DNA integrity Genes altered in cancer typically:


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