Genetics 4 (Cancer) Flashcards
What are the normal functions of tumour suppressor genes?
- Regulate cell division
- Regulate apoptosis
- Regulate DNA Repair
- Monitor DNA damage checkpoint
- TSG is recessive
What is the two hit hypothesis?
- 2 genetic changes (hits) to cause cancer
- first hit (mutation) reduces protein/transcript level
- second hit (larger deletion) removes other allele function of gene completely
What is ‘haploinsufficiency’?
- only takes one hit to give the cell a selective advantage - 50% decrease in protein is sufficient to give cell a selective advantage
What is a common manifestation of the second hit in the 2 hit hypothesis?
- Loss of heterozygosity
- deletion could remove other genes that are part of a heterozygous pair
- the gene appears homozygous as one allele has been lost
What genes predispose to breast and ovarian cancer and what is the lifetime risk?
- BRCA1 and BRCA2
- 60%
What is the patho-genetic mechanism of BRCA genes?
- BRCA genes are DNA repair genes (homologous recombination)
- When the genes mutate, DNA repair proteins are impaired
- dysfunctional DNA repair proteins produced which cause further mutations
What are two diseases that predispose to colorectal cancer and what are the relative risks?
- Familial Adenomatous Polyposis: nearly 100%
- Hereditary Non-Polyposis Colorectal Cancer (HNPCC): 80%
What are ‘cytogenic changes’?
Visible changes in chromosome structure or number
How can a translocation cause cancer?
leads to formation of new fusion gene that encodes a protein with oncogenic properties
How is Chronic Myeloid Leukaemia caused?
- Translocation between chromosome 9 and 22
- BCR gene from chromosome 22 and ABL gene from chromosome 9 fuse in newly formed Philadelphia chromosome
- BCR-ABL fusion gene encodes BCR-ABL1 tyrosine kinase, which promotes CML
What is a targeted therapy for CML and how does it work?
- Imatinib
- blocks ATP binding site of tyrosine molecule
- inhibits BCR-ABL1 tyrosine kinase
What are the three techniques of quantifying the level of CML in order of sensitivity?
- Cytogenetic analysis
- FISH (Fluorescence in situ hybridisation)
- RT-qPCR (Reverse Transcriptase Quantitative PCR)
What is the point of pharmacogenomics?
Uses genetics to determine which patients will respond best to particular treatments
What are the differences between somatic and germline mutations?
- germline: inherited, gametes, hit 1
- somatic: non-inherited, body cells, spontaneous, hit 2
What are the 3 different types of point mutations?
- silent: change in base but triplet still codes for same AA
- missense: change in codon, different protein coded for and structure changes
- nonsense: mutated codon becomes stop codon (makes truncated protein)
