Tumour Pathology 5 Flashcards
What is carcinogenesis due to?
Geographic and environment factors
Age
Heredity
What are the 2 categories of normal genes that can be disrupted and cause cancer?
Tumour suppressor genes (anti-oncogenes)
Proto-oncogenes
What are tumour suppressor genes?
Normal growth inhibitor genes that regulate:
Mitosis (Rb)
Apoptosis (p53)
DNA repair
What are anti-oncogenes also known as?
Tumour suppressor genes
What does p53 regulate?
Apoptosis
What is a key event in tumour formation?
Uncontrolled proliferation, due to cell cycle dysfunction, due to loss of tumour suppressor gene function
What are other mutations that can directly impact the performance of pRb?
CKD4
Cyclin D
CDKIs
What does absent or inactive pRb do?
Releases the brake on the cell cycle, causing cell proliferation
What are the causes of retinoblastomas?
Sporadic
Inherited
What are examples of inherited predispositions to cancer?
Familial retinoblastoma
Familial adenomatous polyposis of colon
Multiple endocrine neoplasia
Neurofibromatosis
Van Hippel-Lindou Syndrome
What are some known inherited mutations of anti-oncogenes?
APC
p53
Rb
p16
BRCA1/2
What does an inherited mutation of APC cause?
FAP colon cancer
What does an inherited mutation of Rb cause?
Retinoblastoma
What does an inherited mutation of p16 cause?
Malignant melanoma
What does an inherited mutation of BRCA1/2 cause?
Breast cancer
What is the function of APC?
Signal transduction
What is the function of p16?
Cell cycle/apoptosis after DNA damage
What is the function of Rb?
Cell cycle regulation
What is the function of p16?
Inhibits CDKs
What is the function of BRCA1/2?
DNA repair
What are proto-oncogenes?
Normal genes coding for normal proteins that regulate growth
What are some functions of proto-oncogenes?
Growth factors
Growth factor receptors
Signal transduction
What are oncogenes derived from?
Proto-oncogenes
What are oncogenes activated by?
Alteration of proto-oncogene structure
Dysregulation of proto-oncogene expression
What can cause an alteration of proto-oncogene structure?
Point mutation
Chromosome rearrangements and translocation
What do oncogenes generate?
Active oncogene products
What are active oncogene products?
Growth factors
Growth factor receptors
Proteins involved in signal transduction
Nuclear regulatory proteins
Cell cycle regulators
How many copies of an oncogene do you need to cause cause?
Only one, not two
What is the process of viral carcinogenesis?
1) Virus inserts genome near a host proto-oncogene
2) Viral promoter or other transcription regulation element cause proto-oncogene overexpression
What is the relationship between reteroviruses and carcinogenesis?
Reteroviruses insert an oncogene into host DNA causing cell division
What are some viruses that are known to cause cancer?
HPV
Hepatisis B
EBV
What cancer does HPV cause?
Cervical cancer
What cancer does Hepatitis B cause?
Liver
What cancer does EBV cause?
Burkitt lymphoma
What is the process of chemical carcinogenesis?
1) Chemicals react with DNA to form covalently binded products known as DNA adducts
2) Leads to activation of oncogenes and suppression of tumour suppressor genes
What is formed when chemicals bind to DNA in chemical carcinogenesis?
DNA adducts
How many steps are necessary for carcinogenesis?
More than one step, a series of mutations is required
How does the number of mutations change as time goes on?
Mutations accumulate
