Chromosomes, Cancer and the Cancer Genome Flashcards
1
Q
What are the features in cancer genome
A
- aneuploidy
- copy number changes
- double minutes
- chromothripsis
- translocation
- telomeres
- point mutations
- epigenetics
2
Q
CIN
A
- loss, gain or rearrangements of chromosomes
- prognostic hallmark of solid and haematological cancers
- cause or effect of carcinogenesis
- thought to arise through errors in chromosome duplication and or segregation
3
Q
What are the two types of CIN
A
- Numerical - gain or loss of whole chromosomes
- structural - gain or loss of individual chromosomal regions
4
Q
What is aneuploidy
A
- deviation from normal number of chromosomes
- common in cancer
- defects in chromosome segregation in cell division
5
Q
What are copy number alterations
A
- regions within chromosomes which are lost
6
Q
What does double minutes mean?
A
- extrachromosomal circular fragments
- replicate in the nucleus
- lack centromere and telomeres
- not rare - found in 50%
7
Q
What is chromothripsis?
A
- mechanism which gives rise to double minutes
- chromosome shattering and random reassembly
- loss of key regions
8
Q
Describe translocations
A
- one chromosomal region is moved from one region to another chromosome
- two forms : balanced or imbalanced
9
Q
What are fusion genes?
A
- hybrid genes, formed from two separate genes
- sometimes lead to functional proteins with oncogenic properties
- eg. BCR-ABL and the philadelphia chromosome
10
Q
Describe Gleevec/Imatinib
A
- introduced in the 1990s
- 5 year CML survival before gleevec = 30%
- 5 year survival with gleevec = 89%
- can only be used in Ph+ cancers
11
Q
Describe inversions with an example
A
- EML4-ALK fusion gene
- EML4 and ALK inverted
- can give rise to solid tumour
12
Q
What drug targets ALK?
A
- crizotinib
- approved after phase 1 trial
- 82 patients, ALK rearranged lung cancer
response rate : 57% (expt. 10%)
13
Q
Describe telomeres
A
- repetitive sequences at chromosome ends
- protect chromosome against fusion
14
Q
What is the end replication problem?
A
- telomeres role to fix
- during each cell division, small part of chromosome at the ends are lost
- when telomere becomes too short, (critical point) cell recognises and induced apoptosis
15
Q
What is telomerase?
A
- ribonucleoprotein : protein - reverse transcriptase (TERT), RNA template (TERC)
- maintain telomeres, enables cell survival
- active in stem cells, inactive in somatic cells
- active in 90% of cancers
- cancer cells escape the apoptotic signal which usually kicks in after certain number of cell divisions
