Tumour Pathology 5 Flashcards
What is the normal function of tumour-suppressor genes?
Normal growth-inhibiting genes - genes negatively regulate mitosis, genes that regulate apoptosis and DNA repair.
What is the normal function of oncogenes?
Normal genes that promote normal cell growth and mitosis.
What is the key event in tumour formation?
Uncontrolled cell proliferation via cell cycle dysregulation via loss of tumour suppressor gene function.
What do Rb gene mutations favour?
Cell proliferation
What do mutations in other genes controlling pRb phosphorylation do?
They mimic the effect of pRb loss.
What does absent or inactive pRb do?
Releases the cell cycle brake.
What is an anti-oncogene?
Retinoblastoma gene
What is the inherited form (two-hit hypothesis)?
One defective inherited copy of pRb and a somatic point mutation of another copy.
What is the sporadic form (two-hit hypothesis)?
Both hits happen sporadically in a single cell.
What types of heredity carcinogenesis are there?
Inherited cancer syndromes, familial cancers, autosomal recessive syndromes of defective DNA repair.
What are the characterstics of an inherited cancer syndrome?
A strong family history of uncommon site-specific cancers, or, autosomal dominant inheritance of a single mutant gene.
Which condition has a 100% risk of colon cancer by age 50?
Familial adenomatous polyposis (FAP)
What can be factors to do with familial cancers?
Family clustering of cancers but individual predisposition unclear, multifactoral inheritance, early age of onset, multiple/bilateral tumours.
What are examples of familial cancers?
Some breast/ovarian cancers, non-FAP colon cancers.
What are proto-oncogenes?
Normal genes coding for normal proteins that regulate growth.
What are onco-genes derived from?
Proto-oncogenes
What are active oncoprotein products?
Growth factors, growth factor receptors, proteins involved in signal transduction, nuclear regulatory proteins and cell cycle regulators.
How are oncogenes activated?
Mutations, increase in certain proteins and translocations including overexpression and recombination to form hybrid proteins
What mechanisms cause viral carinogenesis?
- Virus genome inserts near host proto-oncogene
- Viral promotor can cause proto-oncogene overexpression
- Retroviruses insert oncogene into host DNA causing cell division
What happens during chemical carcinogenesis?
A chemical forms an adduct at particular chromosome sites lead to activation of oncogenes and suppression of anti-oncogenes
What is meant by multi-step carcinogenesis?
Abnormalities accumulate with time, activation of several oncogenes and loss of two or more anti-oncogenes (most cancers)
What is key to malignant transformation?
Loss of cell cycle control
What are some key regulators that are mutated in the majority of cancers?
P16, cyclin D, CDK4, Rb
What does loss or mutations of p53 result in?
Allows genetically damaged cells to proliferate forming malignant neoplasms
