Cancer 3: Biology of Cancer Flashcards
what are the 3 cancers that have been used to study cancer?
Retinoblastoma, tumour suppressor genes and “hereditary” cancer
Breast cancer, genetic risk, screening and “synthetic lethality”
Chronic myeloid leukaemia, oncogenes, “Philadelphia chromosome” and targeted therapy
define mutation
a structural change in DNA that can be transmitted to daughter cells
what are the key features of retinoblastoma?
rare childhood cancer
familial form (40%) and sporadic form (60%)
familial form affects younger children and is often bilateral
sporadic form is unilateral
tumour caused by mutations in Rb tumour suppressor gene
describe how familial retinoblastoma occurs?
child inherits germline copy of mutant Rb gene
every retinal cell bears this mutant allele
probability of spontaneous mutation in other allele high
Rb cancers at young age, bilateral, may be multifocal
how does sporadic retinoblastoma occur?
spontaneous mutations of both copies of the Rb gene must occur in the same retinal cell for tumour to occur
very low probability of this occurring
what does the rb gene encode?
Rb gene encodes retinoblastoma protein pRb
regulates cell cycle progression
what is BRCA1?
large nuclear protein
cell cycle checkpoint signaller
transcriptional regulation
involved in repair of DNA double strand breaks
what is BRCA2?
large nuclear protein
involved in repair of DNA double strand breaks
how is risk defined in BC?
low risk = population risk less than 3% aged 40 - 50 lifetime risk less than 17% moderate risk: 3-8% aged 40 - 50 lifetime risk 17-30% high risk: greater than 8% aged 40 - 50 lifetime risk greater than 30%
how do we manage patients depeding on their risk?
low risk = population risk mammographic screening from age 50 breast awareness, lifestyle information moderate risk: age <40: information, counselling age 40-49: annual mammography high risk: refer to specialist clinic, genetic counselling genetic testing IF affected family member agrees
what are the high risk factors for BC?
family history two relatives with BrCa < 50 yrs three relatives with BrCa < 60 yrs four relatives with BrCa any age ovarian cancer + BrCa < 50 bilateral BrCa < 50 male BrCa + BrCa < 50 Jewish ancestry multiple cancers at young age
how do we reduce the risk if women test positive for BRCA1/BRCA2?
prophylactic treatment surgical breasts ovaries medical
surveillance
mammography, MRI
CA-125
ultrasound pelvis
define synthetic lethality
Synthetic lethality occurs when the simultaneous perturbation of two genes results in cellular or organismal death.
what are 2 clinical features of CML
high WCC
splenomegaly
what is the philadelphia chromosome
transolaction aka t(9;22)
