Genes and Cancer Flashcards
What is metastasis?
When cancerous cells enter blood vessels or lymphatics and spread to different sites around the body
What is carcinogenesis? What is it driven by?
The process of cancer formation. Driven by mutations and in some somatic tissues epigenetic changes
What is hyperplasia?
Cell dividing more rapidly than usual - it is not cancer, it can be a normal response to certain stimuli
What is dysplasia?
Cells change form - it is not cancer, can be a normal response to certain stimuli
What is meant by ‘tumours are monoclonal’?
All the tumour cells descend from a single starting cell (does not mean all tumour cells are identical!)
What are the two types of mutations that arise in tumour cells?
Driver gene mutations
Passenger mutations
Define passenger mutation
Mutation with no direct or indirect effect on selective growth advantage of the cell in which it occurred
Define driver gene mutation
Mutation that directly or indirectly confers a selective growth advantage to the cell in which it occurs
What is the general ratio of driver:passenger mutations an adult tumour may have?
5-8 : hundreds
Driver:Passenger
Where are the three main checkpoints in the cell cycle?
What do they check?
Restriction point (start transition, before moving out of G0): Is environment favourable for division?
G2/M transition: Is all DNA replicated? Is environment favourable for division?
Metaphase to anaphase transition: Are all chromosomes properly attached to the spindle?
What is the M-Cdk?
Cyclin B with Cdk1
What id the S-Cdk?
Cyclin A with Cdk2
What is the G1/S-Cdk?
Cyclin E with Cdk2
What is the G1-Cdk?
Cyclin D with Cdk 4 and/or Cdk 6
Which Cdk does cyclin B bind with?
Cdk1
Which Cdk does cyclin A bind with?
Cdk2
Which Cdk does cyclin E bind with?
Cdk2
Which Cdk does cyclin D bind with?
Cdk4 and Cdk6
What are the main cyclins involved in the cell cycle? Which stages do they control?
Cyclin D [G1]
Cyclin E [G1/S transition]
Cyclin A [S]
Cyclin B [Mitosis]
What type of residues do Cdks have?
Serine / threonine kinases
What activates a Cdk’s kinase activity?
Being bound to its cyclin
Describe Cdk protein levels throughout the cell cycle
Protein levels are relatively constant throughout cell cycle. Their activities rise and fall governed by cyclin interactions
Gene encoding EGFR is mutated in what percentage of brain tumours, breast cancers and ovarian cancers?
40-50% brain tumours
20% breast cancers
15-30% ovarian cancers
CCND1 gene (encodes cyclin D) is mutated in what percentage of oesophageal carcinomas, bladder cancers, and breast cancers??
CCND1 gene is amplified in 35% of oesophageal carcinomas, 15% of bladder cancers and 15% breast cancers
What age group does retinablastoma affect?
Children from birth to 4 years
How is retinablastoma screened for in the UK?
White light shone in eye.
Reflection from normal retina appears red.
White reflection may indicate retinablastoma.
What percentage of children worldwide with retinablastoma die?
87%
Almost exclusively in countries lacking robust screening systems
What is retinablastoma? (disease)
Most common eye tumour in children, affecting 1/20000 children. Arises in immature rapidly dividing retinal cells.
What percentage of cases of retinablastoma are sporadic with no family history? How does it present?
60% of cases are sporadic, unilateral single tumours in one eye
What percentage of cases of retinablastoma are hereditary? How does it present?
40% of cases are hereditary, with multiple tumours, bilateral in both eyes
Disease appears dominant (though actual allele is recessive, its HIGHLY likely to get it because every cell only needs one allele to mutate now to become homozygous recessive [LOH])
