Lecture 10 - Neoplasia III Flashcards
what are 3 examples of inherited susceptibility to development of tumours?
retinitis pigmentosum
ataxia telangiectasia
fanconi’s anaemia
how does retinitis pigmentosum increase susceptibility to tumours?
increased risk of skin cancers when exposed to uv rays in sunlight
how does ataxia telangiectasia increase susceptibility to tumours?
defective response to radiation damage
profound susceptibility to lymphoid malignancies
usually die before 20
how does fanconi’s anaemia increase susceptibility to tumours?
sensitivity to dna cross linking agents, marrow hypo function and multiple congenital anomalies
predisposition to cancer
which gene inheritance causes familial adenomatous polyposis?
apc
which gene inheritance causes breast cancer?
brca 1/2
which gene inheritance causes li fraumeni syndrome?
p53
what is a proto oncogene?
a normal gene that can become an oncogene due to mutations or increased expression
what is the dna sequence of a proto oncogene?
identical to viral oncogenes
how do proto oncogenes become oncogenes?
mutation, amplification, translocation
what are the products of oncogenes?
oncoproteins
what is the significance of oncogenes?
cell can escape normal growth contro
lbecomes self sufficient - doesnt require external signals for growth
how many alleles of a proto oncogene need to mutate to cause neoplasia?
one
what is a tumour suppressor gene?
a gene that encodes proteins that suppress growth and therefore cancer
what is the result of loss or alteration of tumour suppressor genes?
loss of growth suppression
how many alleles of a tumour suppressor genes need to mutate to cause neoplasia?
two
list three oncogenes
rasc-mycher-2
what is the role of the ras oncogene?
normally transmits growth promoting signals to nucleus
mutant ras is permanently activated - continuous stimulation of cells
15-20% of all cancers
colon and lung cancer
what is the role of the c-myc oncogene?
binds to dna, stimulates synthesis
amplified –> neuroblastoma, breast cancer
translocation from 8 to 14 –> burkitts lymphoma
what is the role of the her-2 oncogene?
encodes for a growth factor receptor
amplified
25% of breast cancers
what is a competitive antagonist at the her-2 receptor?
herceptin
list two tumour suppressor genes
pRb
p53
what is the role of pRb?
passage beyond R checkpoint at G1/S boundary is governed by phosphorylation of pRb
defect in both alleles leads to cell escaping cell cycle control
retinoblastoma
what is the role of p53?
approx 50% of tumour contains p53 mutations
gene encodes a nuclear protein which binds to and modulates expression of genes important for cell cycle arrest, dna repair and apoptosis
describe the initiator stage of carcinogenesis
- exposure of cells to sufficient dose of initiator
- cell is altered, potentially capable of producing a tumour
- permanent dna damage
- irreversible and has memory
- effect modified by genetic factors
- initiation is not sufficient for tumour formation
describe the promoter stage of carcinogenesis
- can induce tumours in initiated cells
- non tumourigenic on their own
- need exposure after initiation
- cellular changes are reversible if remove promoter
- enhance proliferations, especially in mutated cells and increase incidence of further mutations
how does radiation contribute to tumour development?
dna damage:
single strand break
double strand break
base damage
what is the effect of radiation dependent on?
quality of radiation
dose
give two types of radiation
ionising
ultraviolet
how do chemicals contribute to tumour development?
act directly
require metabolic conversion to an active form
give three examples that contribute to tumour development
polycyclic aromatic hydrocarbons
aromatic amines
alkylating agents
how do polycyclic aromatic hydrocarbons contribute to tumour development?
produced in combustion of tobacco and fossil fuel
hydroxylated to active form
lung cancer, bladder cancer, skin cancer
how do aromatic amines contribute to tumour development?
hydroxylated in liver and conjugated with glucorinic acid
deconjugated to active form in urinary tract by urinary glucuronidase
active form sits in bladder –> bladder cancer
rubber and dye workers
how do alkylating agents contribute to tumour development?
bind directly to dna
nitrogen mustard
give three viruses that contribute to tumour development
hep b
epstein barr
human papilloma
how does hep b contribute to tumour development?
associated with hepatocellular carcinoma
viral dna integrated into host cell genome
virus causes liver cell injury –> regenerative hyperplasia
increased cell division gives increased risk of genetic changes
how does epstein barr contribute to tumour development?
implicated in pathogenesis of burkitts lymphoma, some hodgkins lymphoma and nasopharyngeal carcinoma
infects epithelial cells or oropharynx and B cells
viral genes dysregulate normal proliferative and survival signals
sets the stage for acquisition of mutations
how does human papilloma contribute to tumour development?
hpv genes disrupt normal cell cycle
viral genes incorporated into host cell genome, driving proliferation
give five other agents that contribute to tumour development
asbestos aflatoxins schistosoma helicobacter hormones
what does asbestos cause?
malignant mesothelioma
lung cancer
what do aflatoxins cause?
hepatocellular carcinoma
what does schistosoma cause?
bladder cancer
what does helicobacter cause?
gastric cancer
lymphoma
what do hormones cause?
androgens
hepatocellular carcinoma
give three conditions that predispose tumours
ulcerative colitis
cirrhosis
adenoma of colon/rectum
