1. Tumor Viruses
Oncogenes &
Tumor Supressor
genes
Adapted from The Biology of Karobi Moitra (Ph.D)
Cancer
First Edition
NCI Frederick , NIH
Cancer Inflammation Program
Robert A. Weinberg
Human Genetics Section
Chapter 3, 4 & 7
Frederick MD.
MD.
Copyright © Garland Science 2007

2. Peyton Rous and Rous Sarcoma Virus (RSV)
1910 1966
Figure 3.1 The Biology of Cancer (© Garland Science 2007)

3. 1909 Rous’s Protocol for inducing breast sarcomas in chicken
Viruses can cause cancer in chickens !
Figure 3.2 The Biology of Cancer (© Garland Science 2007)

5. The Virion (virus particle) of RSV and other related viruses:
RNA viruses (retroviruses) can cause cancer
Figure 3.4a The Biology of Cancer (© Garland Science 2007)

6. Structure of the RSV genome
ALV = Avian leukosis virus Oncogene
Figure 3.19 The Biology of Cancer (© Garland Science 2007)

7. The Double Helix

8. RNA vs DNA

9. The Virion (virus particle) of RSV and other related viruses:
RNA viruses (retroviruses) can cause cancer
Figure 3.4a The Biology of Cancer (© Garland Science 2007)

10. RNA to DNA
Reverse transcription
with the enzyme
reverse transcriptase

11. The flow of genetic information- the central dogma

12. Murine (mouse) Leukemia Virus particles budding from an infected cell
Figure 3.4b The Biology of Cancer (© Garland Science 2007)

13. Normal cells can be converted into tumor cells (transformation)
Figure 3.7a The Biology of Cancer (© Garland Science 2007)

14. Normal cells can be converted into tumor cells (transformation) :
RSV can transform infected cultured cells (in a petri dish)
An RSV induced Foci
CALTECH:
Dulbecco,Rubin & Temin
Figure 3.5 The Biology of Cancer (© Garland Science 2007)

15. Some viruses can transform normal cells
1910 1966
Nobel prize in
Physiology and medicine

16. DNA Viruses can also induce cancer
Shopes virus
Richard Shope
Figure 3.9a The Biology of Cancer (© Garland Science 2007)

17. HPV = Human papilloma virus - A DNA tumor virus
Figure 3.9b The Biology of Cancer (© Garland Science 2007)

18. Table 3.1 The Biology of Cancer (© Garland Science 2007)

19. Oncogenes were first discovered in viruses
and called v-oncs , viral oncogenes

20. Oncogenes &
Proto-oncogenes

21. Genes and Cancer
Viruses
Chemicals Radiation
Heredity
Chemicals (e.g., from smoking), radiation, viruses, and Chromosomes
heredity all contribute to the development of cancer by are DNA
triggering changes in a cell’s genes molecules

22. Oncogenes or tumor genes are genes with potential properties for the
induction of neoplastic transformation
(either in natural or experimental conditions)
(Duesberg 1980)
Normal cellular genes with the potential to become oncogenes
are called proto-oncogenes

23. Proto-oncogene Oncogene

24. Proto-Oncogenes and Normal Cell Growth
Normal Growth-Control Pathway
Growth factor
Receptor
Signaling enzymes
Transcription
factors
Cell nucleus DNA
Cell proliferation
Oncogenes are related to normal genes called proto-oncogenes that encode components of the cell’s normal
growth-control pathway. Some of these components are growth factors, receptors, signaling enzymes, and
transcription factors. Growth factors bind to receptors on the cell surface, which activate signaling enzymes
inside the cell that, in turn, activate special proteins called transcription factors inside the cell’s nucleus. The
activated transcription factors “turn on” the genes required for cell growth and proliferation.

25. Normal cell Normal
genes
regulate
cell growth
Oncogenes
Cancer cell accelerate
cell growth
and division
Oncogenes are genes whose PRESENCE in
Mutated/damaged oncogene certain forms and/or overactivity can
stimulate the development of cancer.

26. Oncogenes or tumor genes are genes with potential properties for the
induction of neoplastic transformation
(either in natural or experimental conditions)
(Duesberg 1980)
The word oncogene comes from the word ‘onkos ‘ meaning tumor

27. When a proto-oncogene becomes activated it is
called an oncogene

28. Proto-oncogene Oncogene

29. When an oncogene becomes activated it might
cause cancer
Proto-oncogene -> oncogene -> other steps -> cancer

30. Activation of Oncogenes
1. Mutation
a. Insertional mutagenesis
b. Point mutagenesis
2. Amplification
3. Translocation

31. Mutation : A mutation is a permanent change in
the DNA sequence of a gene. Mutations in a
gene's DNA sequence can alter the amino acid
sequence of the protein encoded by the gene.

32. 1a. Insertional Mutagenesis
ALV provirus may become integrated with the c-myc oncogene
ALV switches on c-myc
Figure 3.23b The Biology of Cancer (© Garland Science 2007)

33. Activation of oncogenes
1b. Mutagenesis of oncogenes
Altered polypeptides produced by mutant oncogenes could be
related to the origin of some human tumors

34. Activation of oncogenes
Mutation responsible for H-ras oncogene activtion
Human bladder cancer oncogene - 12th codon of H-ras ,mutation
converts glycine codon to valine codon
Figure 4.10 The Biology of Cancer (© Garland Science 2007)

36. Activation of oncogenes
2. Amplification of oncogenes
More than one copy of a gene:
Amplification

37. Activation of oncogenes
The N-myc gene is often amplified in human childhood
neuroblastomas
FISH - showing amplification
of N-myc to produces HSR’s
homogeneous staining regions
(chromosome 2)
Figure 4.11a The Biology of Cancer (© Garland Science 2007)

38. How are oncogenes amplified?
Double minute chromosomes

39. Activation of oncogenes
3. Translocation
A chromosome translocation is a chromosome A karyotype is the number and appearance
abnormality caused by rearrangement of parts of chromosomes in the nucleus of a
between nonhomologous chromosomes. A gene eukaryote cell
fusion may be created when the translocation
joins two otherwise separated genes, the
occurrence of which is common in cancer.

40. Burkitts lymphoma t(8;14) the c-myc gene is placed under the
control of the enhancer sequence of an immunoglubulin gene
Figure 4.13a The Biology of Cancer (© Garland Science 2007)

41. Reciprocal translocations between human Chr 9 (abl) and 22 (bcr)
Fusion protein
Bcr-abl oncogene formation gives rise to acute lymphocytic leukemia
(ALL),chronic myelogenous leukemia (CML) or chronic
neutrophillic leukemia (CNL)
Figure 4.15a The Biology of Cancer (© Garland Science 2007)

42. Activation of Oncogenes
1. a. Insertional mutagenesis
b. Point mutagenesis
2. Amplification
3. Translocation

44. Tumor Suppressor Genes

45. Tumor Suppressor Genes
Tumor suppressor genes are normal genes whose ABSENCE
can lead to cancer
i.e. Tumor suppressor genes protect the cell

46. Tumor Suppressor Genes - Tumor suppressor genes are normal genes whose ABSENCE can lead to cancer
i.e. Tumor suppressor genes protect the cell
Normal cell Normal
genes
prevent
cancer
Remove or inactivate
tumor suppressor genes
Cancer cell Damage to
both genes
leads to
cancer
Mutated/inactivated If a pair of tumor suppressor genes are either
tumor suppressor genes lost from a cell or inactivated by mutation,
their functional absence might allow cancer
to develop

47. Tumor Suppressor Genes
Act Like a Brake Pedal
Tumor Suppressor
Gene Proteins
Growth factor
Receptor
Signaling
enzymes Transcription
factors
Cell nucleus DNA
Cell proliferation
Tumor suppressor genes are a family of normal genes that instruct cells to produce proteins that restrain cell growth and division. Since tumor
suppressor genes code for proteins that slow down cell growth and division, the loss of such proteins allows a cell to grow and divide in an
uncontrolled fashion. Tumor suppressor genes are like the brake pedal of an automobile. The loss of a tumor suppressor gene function is like
having a brake pedal that does not function properly, thereby allowing the cell to grow and divide continually.

48. Tumor suppressors act similar to the ‘brakes’ of a car (analogy)

49. p53 Tumor Suppressor Protein
Triggers Cell Suicide
p53 protein
Normal cell Excessive DNA damage Cell suicide
(Apoptosis)
One particular tumor suppressor gene codes for a protein called “p53” that can trigger cell suicide (apoptosis). In cells
that have undergone DNA damage, the p53 protein acts like a brake pedal to halt cell growth and division. If the damage
cannot be repaired, the p53 protein eventually initiates cell suicide, thereby preventing the genetically damaged cell
from growing out of control.

50. pRB - Tumor suppressor gene
From R Bernards

51. Petite arm
(small)
NLM

52. Retinoblastoma occurs when pRB is mutated (inactivated)
or sometimes deleted
Figure 7.4b The Biology of Cancer (© Garland Science 2007)

53. Inherit mutant
allele
Figure 7.7 The Biology of Cancer (© Garland Science 2007)

54. Deletion of a part of Chromosome 13 in a retinoblastoma patient
Figure 7.10 The Biology of Cancer (© Garland Science 2007)

55. Oncogenes or tumor genes are genes with potential properties for the
induction of neoplastic transformation either in natural
or experimental conditions
(Duesberg 1980)
Tumor suppressor genes are normal genes whose ABSENCE
can lead to cancer

56. “Never, never, never give up”
Winston Churchill
1966
Nobel prize in
Physiology and medicine