L4: ONCOGENES I [03/10/2022]
I. CANCER IS A GENETIC DISEASE
Oncogenes:
PRESENCE in altered or excessive forms contributes to cancer
Mutated forms lead to over-active or too much protein
Involved in growth control
Tumour Suppressor Genes:
ABSENCE can contribute to cancer
Restrain cell growth and division
Often involved n inherited predisposition to cancer
II. HOW ARE ONCOGENES INDENTIFIED?
Knock in and knock out
Oncogenes: “A gene that causes the transformation of normal cells into cancerous tumour cells”,
also defined as “Mutated and/or over-expressed version of normal gene, that in a dominant
fashion releases the cell from normal growth restraints”
Oncogenes gains a function:
- A proto-oncogene is the wild-type allele (normal gene) of an oncogene
- Activating mutation of proto-oncogene creates the oncogene
- One allele usually only affected = DOMINANT
III. HISTORICAL EVIDENCE
1911: Rous isolated virus from spontaneous chicken sarcomas
1914: Theodore Boveri experimented on the development of double-fertilised sea-urchin
eggs and later suggested that malignant tumours might be result of a certain abnormal
condition of chromosomes, which may arise from the multipolar mitosis.
1960: Nowell & Hungerford – evidence form casual role for genomic rearrangement
1969: Huebner & Todaro – proposed viral genes: integrated into genome; dominant
/activated; malignant transformation
Stehelin et al., - demonstrated the RSV contained sequence not found in related, but non-
transforming retrovirus. Viral sequence was related to sequence in DNA of normal chicken
IV. MECHANISMS OF TRANSFORMATION BY RETROVIRUSES
, We can identify oncogenes through retroviruses
Humans do not have many viruses that cause cancers but more in animals and other species
V. DNA TUMOUR VIRUSES: ‘viral oncogenes’
SV40 Large T antigen: binds and inactivates p53 – growing evidence of SV40 in brain cancers,
NHL, lymphoma, and mesothelioma
Adenovirus E1A: binds pRb and immortalises cells
E1B (55K) inactivates p53
HPV E6: interacts with p53 and activates telomerase
E7: interacts with pRb
- HPV 16, 18, 31, 33, 45 found in >99% of all cervical cancer
- Vaccination for HPV to prevent cervical carcinoma
VI. CANCER HALLMARKS
Q&A: Which of the following statements are true of oncogenes?
a. Proto-oncogenes are the result of mutations in oncogenes
b. Both alleles need to be mutated for oncogenic function to be acquired
c. Mutations causing oncogenes usually result in dominant activities
I. CANCER IS A GENETIC DISEASE
Oncogenes:
PRESENCE in altered or excessive forms contributes to cancer
Mutated forms lead to over-active or too much protein
Involved in growth control
Tumour Suppressor Genes:
ABSENCE can contribute to cancer
Restrain cell growth and division
Often involved n inherited predisposition to cancer
II. HOW ARE ONCOGENES INDENTIFIED?
Knock in and knock out
Oncogenes: “A gene that causes the transformation of normal cells into cancerous tumour cells”,
also defined as “Mutated and/or over-expressed version of normal gene, that in a dominant
fashion releases the cell from normal growth restraints”
Oncogenes gains a function:
- A proto-oncogene is the wild-type allele (normal gene) of an oncogene
- Activating mutation of proto-oncogene creates the oncogene
- One allele usually only affected = DOMINANT
III. HISTORICAL EVIDENCE
1911: Rous isolated virus from spontaneous chicken sarcomas
1914: Theodore Boveri experimented on the development of double-fertilised sea-urchin
eggs and later suggested that malignant tumours might be result of a certain abnormal
condition of chromosomes, which may arise from the multipolar mitosis.
1960: Nowell & Hungerford – evidence form casual role for genomic rearrangement
1969: Huebner & Todaro – proposed viral genes: integrated into genome; dominant
/activated; malignant transformation
Stehelin et al., - demonstrated the RSV contained sequence not found in related, but non-
transforming retrovirus. Viral sequence was related to sequence in DNA of normal chicken
IV. MECHANISMS OF TRANSFORMATION BY RETROVIRUSES
, We can identify oncogenes through retroviruses
Humans do not have many viruses that cause cancers but more in animals and other species
V. DNA TUMOUR VIRUSES: ‘viral oncogenes’
SV40 Large T antigen: binds and inactivates p53 – growing evidence of SV40 in brain cancers,
NHL, lymphoma, and mesothelioma
Adenovirus E1A: binds pRb and immortalises cells
E1B (55K) inactivates p53
HPV E6: interacts with p53 and activates telomerase
E7: interacts with pRb
- HPV 16, 18, 31, 33, 45 found in >99% of all cervical cancer
- Vaccination for HPV to prevent cervical carcinoma
VI. CANCER HALLMARKS
Q&A: Which of the following statements are true of oncogenes?
a. Proto-oncogenes are the result of mutations in oncogenes
b. Both alleles need to be mutated for oncogenic function to be acquired
c. Mutations causing oncogenes usually result in dominant activities
