1. Cancer

2. All cells have the capacity to become cancerous
Misusing Normal Tools
Using Abnormal “super tools” or
“broken
tools”
All cells have the capacity to become cancerous

3. Cancers are categorized

4. Categorization of Cancers
Sarcoma
Carcinoma

8. Blood Cancers
Myeloid Leukemias
Lymphoid Leukemias

9. Neural Tissue Cancers

10. Cancers develop gradually

11. normal
metaplasia

12. Hyperplasia

13. Pre-Cancer

15. Epithelial  Mesenchymal Transition (EMT)

16. Metastasis

17. Cancers don’t affect everyone equally

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

22. Cancers result from alternations in DNA structure or utilization
Sometimes the DNA is mutated, and other times it’s not…

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

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

25. Proto-oncogenes  Oncogenes

26. Conversion of a Proto-oncogene  an Oncogene
Change gene expression / Change protein production
(Produce TOO MUCH)

27. Increase promoter utilization by HYPO-METHYLATION

28. Increase promoter utilization by
POINT MUTATION

29. Alter the promoter that is used by TRANSLOCATION
Chromosome 14 with translocation
Chromosome 8 with translocation

30. (by transcription or by stabilization)
Increase the amount of
mRNA
(by transcription or by stabilization)
Transcription
Translation

31. Increase the number of copies of a gene

32. Decrease Turnover

33. Conversion of a Proto-oncogene  an Oncogene
Change the function of a gene product
(Produce a “super tool”)

34. DNA Point Mutation

35. DNA Deletion / Protein Truncation

36. Chromosomal Translocation

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

38. Tumor Suppressor Genes

39. Inactivation of a Tumor Suppressor Gene
Change gene Expression

40. Decrease promoter utilization by HYPER-METHYLATION

41. Decrease promoter utilization by HYPER-METHYLATION

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

44. Loss of Tumor Suppressor gene function
Change gene function
(Produce a “broken tool”)

45. 2 x 1 / 106 = 1012
1 / 106

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

47. Inactivating mutation
Point mutation
Insertion
Deletion
Frameshift