Genetic Predisposition to Cancer Flashcards
What are somatic mutations?
Most common form of cancer where cells iwhtin the body, not the germline, develop genetic alterations.
Where do somatic mutations occur?
Occur in nongermline tissues
Are somatic mutations inheritable?
No
Where do germline mutations arise from?
Present in egg or sperm
Are germline mutations inheritable?
Yes and can cause family cancer syndromes.
Describe what is meant by the fact that tumours are clonal expressions.
-A normal cell develops an alteration and then through the daughter cells copying and dividing, more mutations can be acquired.
As more critical mutations arise, you may get a tumour with the potential to metastasise.
Wat are proto-oncogenes?
Normal gene that codes for proteins to regulate cell growth and differentiation.
What changes a proto-oncogene into an oncogene?
Mutations
What can oncogenes do to cell division?
Accelerates the process
How many mutations is sufficient enough for the fomration of cancer?
1
What are Tumour suppressor genes?
The cell’s brakes for cell growth as genes can inhibit the cycle, promote apoptosis or both.
When does cancer occur?
If both Tumour suppressor genes do not function and not not ‘brake’.
How many hits on Tumour suppressor genes does it take for cancer to arise?
2 as two brake mechanisms
(inhibition and apotosis).
What are DNA damage-response genes?
The repair mechanics for DNA
When does cancer arise relating to DNA damage-response genes?
Cancer arises when both genes fail, speeding the accumulation of mutations in other critical genes
What does mismatch repair do?
(
MMR corrects errors that spontaneously occur during DNA replication like single base mismatches or short insertions and deletions
What are microsatellites?
Microsatellites (aka Simple Sequence Repeats SSR) are repeated sequences of DNA, can be made of repeating units of 1 – 6 base pairs
What is MSI?
(Microsatellite instability)
MSI (changes in microsatellite sequences) is the phenotypic evidence that MMR is not functioning normally – genetic hypermutability
Describe benign tumours.
-Lacks ability to metastasize.
-Rarely or never become cancerous.
-Can still cause negative health effects due to pressure on other organs.
Define malignant tumours.
Able to metastasize.
Describe dysplastic tumours.
Benign but could progress to malignancy. Cells show abnormalities of appearance & cell maturation. Sometimes referred to as ‘pre-malignant’.
Give examples of some Dominantly Inherited Cancer Syndromes and then gene process and genes that cause them.
Familial medullary thyroid cancer- RET genes in oncogenes
Breast/ovarian cancer- BRCA1, BRCA2 in tumour suppressor genes
HNPCC / Lynch Syndrome- MLH1, MSH2, MSH6, PMS1, PMS2 in DNA repair/ DNA mismatch repair
What are de novo mutations?
New mutation in an individual present in the germline but not in their parents
What is retinoblastoma?
Most common eye tumour in children
