T2 Cancer Genetics
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Which of the top causes of death has a genetic component?
All can have a genetic component
What is a neoplasm/neoplasia?
Where is a tumor most likely to occur?
in tissues with higher turn over
What is the hallmark of tumors?
- increased rate of cell division or mitosis
- uncontrolled growth
In tissues what is disregarded?
the amount of times a cell can divide
What are the 2 types of neoplasms?
- Benign: doesn't metastasize
- Malignant: does metastasize
- regular pattern, even borders, encapsulated
- resembles tissue of origin (well differentiated)
- goes to distant sites
- irregular patterns no capsule
How do we grade tumors?
- TNM in stages of 0-4
- tumor, nodes, malignancy
What is clonal condition
it only takes one damaged cell
What is hyperplasia?
more cells than normal
Where do benign/malignant tumor grow?
- grow locally and in place
- enter blood vessels and go to places (invades)
how do tumors get to a new location?
- invade surr tissues/blod vessels
- cells transported by circ system
- cells reinvade and grow at new location
How does cancer occur?
oncogene activation and tumor supressor gene inactivation
How many mutations lead to cancer?
- mant somatic mutations
- only takes 3 mutations
- mutations in at least 2 genes
What is oncogenesis?
What is a oncogene?
mutant of normal gene (pro to-oncogene( that codes for normal growth
Tumor Supressor Gene inactivation
tumor suppressor gene--> regulates cell cycle= bad
What are unique about oncogenes
- are in embryo (inactive) everyone has them
- they are normal genes though
- =uncontrolled cell division
What has to happen for cancer to happen?
- 1)mutation of the proto-oncogene = activates oncogenes =increase rate of cell division
- 2) have to inactivate tumor suppressor gene
What is a proto-oncogene?
- controls cell division
- when activated=uncontrolled cell division
Why is proto-onco gene not a good name?
- there is not just one but many and not just on one chromo but on many
- turn off and stay turned off but DNA replication it can stay on
What is a tumor suppressor gene
- regulates cell cycle
- "brake pedal"
What do TSG do?
- keep us healthy
- monitor cells
What are the 2 types of TSG?
- Gate keeper genes: proteins that control cell cycle
- Caretaker genes: proteins that protect DNA
What 4 things do proto-oncogenes do?
What things do TSG do in Caretaker genes?
Proto-onco =1 allele
TSG= needs both alleles need to be mutated **
What is an example of a TSG
- caretaker gene p53 (nuclear phosphoprotein)
- stops cell cycle in G1 when DNA damaged
What happens if the DNA is not repaired?
How many cells are believed to be due to p53 inactivation?
How is p53 inactivated?
missense mutation = cell suicide
What genes causes cell suicide?
What percent are familial cancers?
less than 5% can be passed on
What factors do familial cancers have?
- early onset
- bilateral invol/mulifocal tumors (both lungs/breast)
- two rare tumors
- 2+ relatives with same tumor
What is the most common type of cancer in women?
- breast cancer
- founder effect W/E countries
What is the ratio of breast cancer?
1 in 20 familial
What is BRCA?
- Breast cancer mutations
- tumor suppressor gene mutations
What is the frequency of breast cancer?
Where is BRCA 1 located?
- lifetime cancer risk
Where is the BRCA 2 located?
- breast cancer 60-85%
- ovarian cancer 10-20%
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