aging and disease lecture 4- cancer 1 Flashcards
what is cancer?
when abnormal cells divide in an uncontrolled way. some cancers may eventually invade surrounding cells and they are all genetic diseases
what are the most common cancers? (more than half cases)
-breast
-prostate
-lung
-bowel
when is the highest age range for cancer?
85-89, it reaches a peak at this age for incidence and then it willl decrease over 90
is cancer a genetic disease?
yes, the susceptibility to some cancers is familial. most common mutations are found in cancer
how many independent mutations are required?
5-6
what are germline mutations?
passed from parent through egg or sperm and goes to all cells in the affected offspring, making it heritable which cause cancer family syndromes
what are somatic mutations?
a somatic mutation occur in non-germline tissues, making them nonheritable
what are proto-oncogenes?
genes that encode proteins that stimulate cell proliferation. they are normal cellular gene usually involved in cell growth or cell division
what are tumour suppressor genes?
genes that encode proteins that prevent cell proliferation
what are oncogenes?
a proto-oncogene that has been activated by mutation or over expression. results in a dominant gain of function phenotype, only one copy to be mutated
what is a point mutation?
can convert proto-oncogenes into oncogenes by deletion or point mutation in coding sequence. this results in a hyperactive protein made in normal amounts = uncontrolled growth = cancer
what is gene amplification?
convert proto-oncogenes into oncogene by having extra copies of genes being copied. there is normal protein activity but in large volumes
what is chromosomal rearrangement?
can convert proto-oncogenes into oncogenes by crossing over genes resulting in over production of normal genes or a greatly overproduction of fusion protein
what must a mutation be?
loss of function and recessive so both copies are needed to be mutated
how does a tumour suppressor lose its function?
normally these genes suppress cell division but a mutation causes them to lose their function
what are the 2 types of cancer in knudsons 2 hit hypothesis?
sporadic (no hereditary) and familial (hereditary)
Two mutations (two-hits) are required for loss of tumour suppressor function
The first “hit” is inherited & the second “hit” is somatic
what is retinoblastoma?
the loss of a single gene (Rb) is a key step in developing a tumour of the retina
what happens when non-phosphorylated Rb bound to E2F gets phosphorylated?
-PhosphorylatedRb releases E2F.
-E2F migrates to the nucleus to induce transcription
-Proteins required for cell cycle progression
what is sporadic retinoblastoma?
60% of retinoblastoma cases
Develops in children with no family history
Occurs in one eye
Somatic mutation in one allele
Somatic mutation in other allele
causing single tumour …
what is hereditary retinoblastoma?
40% of retinoblastoma cases
Onset typically earlier than sporadic cases
Multiple tumours involving both eyes
Consistent pedigrees; siblings and offspring develop the same type of tumours
Tumour suppressor gene containing a germline mutation in one allele – heterozygous for the mutation
then a Somatic mutation in other allele
which leads to multiple tumours
what is p53?
-p53 is a transcription factor that regulates the cell cycle, DNA repair and apoptosis
-Is a tumour suppressor gene
-Mutations in p53 are implicated in ~50% of human cancers, including cancers of the breast, lung, colorectal and stomach.
why is there no homozygous. Rb mutants?
homozygous Rb mutants – embryonic lethal
what happens during a norma cell cycle in response to dna?
Tumour suppressors function in many key cellular processes including the regulation of transcription, DNA repair and cell:cell communication.
The loss of function of these genes leads to abnormal cellular behaviour.
what happens in the absence of p53?
cell cycle is not inhibited and increased cell division occurs
what are breast cancer stats?
-15% of cancer cases are breast
-peak age is 90+
where does breast cancer occur?
breast cancer occurs in the cells that line the lobules that manufacture milk or more commonly in the ducts that carry it to the nipple.
what mutation causes most hereditary cases?
BRCA1 and BRC12 mutations. most are causes by sporadic except around 7-10% and BRCA1 is majority cause out that percentage
what do these mutations cause?
-an increase in risk of early onset of breast cancer
what are sporadical and hereditary mutations in breast cancer?
SPORADIC breast cancer:
Older women
One tumour
One breast (unilateral)
FAMILIAL (BRCA1 mutation: heterozygous)
Younger women
Often multiple tumours
Often affects both breasts (bilateral)
what is the function of BRCA1?
BRCA1 protein REQUIRED for normal DNA repair
Loss-of-function:
( up to ~300,000 mutations per cell division)
so losss of function causes an accumulation of mutations= cancer
what is number ~250?
Only a subset mutated in any given cancer type or individual tumour
what is a growth factor?
induces cell proliferation
eg PDGF
what is a receipt tyrosine kinase?
Transduce signals for cell proliferation
eg egfr
what are transcription factors?
Regulate transcription of genes that induce cell proliferation
eg Myc
what is signal transducing proteins?
involved in signalling eg Was
