Carcinogenesis 2 Flashcards
What are the 3 key systems that can become disrupted and can then cause cancer?
- Proto-oncogenes
- Tumor suppressor genes
- Regulators for apoptosis
A mutation of a proto-oncogene leads to the creation of what and leads to what?
- Mutations form oncogenes
- Leads to unregulated cell growth
What are the different categories of oncogenes?
- Growth factors
- Growth factor receptors
- Signal transducers
- Cell cycle regulators
What growth factor is over-expressed in Astrocytoma?
PDGF B
- Platelet Derived Growth Factor B
- Autocrine loop
ERBB2 (HER2 neu) (epidermal growth factor) receptor can be amplified to create what kind of cancer?
Breast cancers
The RET (neural growth factor receptor) can have a point mutation and lead to what cancers?
- MEN 2A
- MEN 2B
- Sporadic medullary carcinoma of the thyroid
The KIT (stem cell growth factor) can have a point mutation and lead to what kind of tumour?
GI stromal tumour
HER2 (growth factor receptor) +ve breast cancer can be treated with what drug?
Trastuzamab
What signal transducers can get mutations and then cause cancer?
- RAS gene family
- ABL
The RAS gene family effects what protein?
GTP-binding protein
A point mutation in RAS (coding for GTP-binding protein) can lead to what cancers?
- Carcinomas
- Melanoma
- Lymphoma
ABL codes for what enzyme?
Tyrosine kinase
What kind of mutation affects ABL?
t(9;22) with BCR
A mutation of ABL (codes for tyrosine kinase) leads to what cancers?
CML
- Some types of adult ALL
(9;22 translocation w. BCR)
What are the nuclear regulators which can mutate and cause cancer?
- c-MYC
- N-MYC
- L-MYC
What kind of mutation affects c-MYC?
t(8;14) involving IgH
A translocation mutation of c-MYC (transcription factor) leads to what cancer?
Burkitt lymphoma
An amplification of N-MYC leads to what cancer?
Neuroblastoma
An amplification of L-MYC leads to what cancer?
Small cell Lung Cancer
What cell cycle regulators can become mutated and cause cancer?
- CCND1 (cyclin D1)
- CDK4
What mutation affects CCND1 (cyclin D1) leading to Mantle Cell Lymphoma?
t(11;14) involving IgH
What cell cycle regulator can become mutated to cause Mantle cell lymphoma?
CCND1 (cyclin D1)
- t(11;14) involving IgH
What cell cycle regulator can become amplified to cause Melanoma?
CDK4 (cyclin-dependent kinase)
What happens with RAS when GF binds to the growth factor receptor?
RAS binds to GTP instead of GDP (bound to in quiescent state)
- RAS-GTP complex allows a message to be sent to nucleus
- RAS take a phosphate off of GTP to become GDP
What does GAP do?
Inactivates RAS
- GDP complex not created anymore
ALL due to a t(9;22) (tyrosine kinase) is known as what?
Ph+ (Philadelphia chromosome +ve) ALL
Burkitt lymphoma is a lymphoma of what cells?
B cells
What do the stars and sky represent in the characteristic ‘starry sky’ appearance of Burkitt lymphoma?
- Macrophages consuming dying cells - stars (white)
- Tumor cells / lymphocytes - blue sky
What sits on the chromosome 14 and chromosome 8 in the 8, 14 translocation - Burkitt lymphoma?
chromosome 8 - Myc
chromosome 14 - IgH
Mantle cell lymphoma is a cancer of what cells?
B cells
Mantle cell lymphoma is due to a translocation of what chromosomes?
Where is cyclin D1 located
Where is igH located?
11 and 14
- 11: Cyclin D1
- 14: IgH
