Chromosomes,cancer and cancer genome

Question 1

Cancer is a disease of the genome

Answer 1

genetic alteration leads to altered protein expression to altered biology

Question 2

features in cancer genomes

Answer 2

aneuploidy
copy number changers
double minutes
chromthripsis
epigenetic
translocation
point mutation

Question 3

Chromosomal instability (CIN)

Answer 3

loss or gain or rearrangement of chromosomes
prognostic hallmark of cancers
thought to arise due to errors in chromosome duplication

Question 4

types of CIN

Answer 4

numerical - gains or loss
Structureal - gain or loss of chromosomal regions

Question 5

Aneuploidy

Answer 5

change in number of chromosomes
common in cancer
due to defects in chromosome segregation

Question 6

copy number alterations

Answer 6

occur across tumour types
whats important is whats in that region being amplified or deleted

Question 7

double minutes

Answer 7

Extrachromasomal circular fragments
replicate in nucleus
lack centromere and telomeres
evolve with tumour

Question 8

chromothripsis

Answer 8

chromsome shattering and random reassembly

Question 9

Translocation

Answer 9

when one chromosomal region is moved to another
can be balanced or imbalanced - depneding on gain or loss of dna material
can cause fusion genes
within a chromsome can cause inversions where you flip a gene inside a chromsome can give fusion genes
drug for this ALK

Question 10

fusion genes

Answer 10

hybrid genes from two seperate ghenes
can lead to functional proteins with oncogenic properties
drug target for drugs like imatinib

Question 11

Telomeres

Answer 11

repetative structure at chromosome end
protect against chromosome fusion
overcome end replication problem - replication cant go all the way to end of chromosome we lose some at each division and telomere prevents this
in cancer they are regenerated by telomerase
active in stem cells and 90% of cancer

ALT
found in 10% of canc
in certain cancers
poor prognosis through chromosome instability
mediated by homologous recomb

Question 12

Point mutations

Answer 12

insertions/deletions(frame shift)
substitution(silent-same amino acid, missense-wrong amino acid, nonsense-introduce stop codon etc).

cancer cells have high mutation burden

Question 13

Cancer is a multistage process

Answer 13

no single mutation is enough
cells accumulate mutations each one can effect different hallmark of proliferation
mutation range is different across different cancers

Question 14

Driver mutation

Answer 14

causally implicated in cancer
if a mutation is commonly scene in cancers it is a driver mutation

Question 15

passenger mutation- does not contribute to cancer

Question 16

functional classes of significantly mutated genes

Question 17

Breast cancer point mutations

Answer 17

thousands of mutations found in breast cancer with around 2/3 missense 1/3 silent and 5% nonsense

Question 18

Epigenetic mechanisms 3 types

Answer 18

DNA methylation
histone modification
non coding RNAs

Question 19

DNA methylation

Answer 19

addition of methyl group by dna methytransferase
repetitive sequences
found in CpG islands in promoters
transcriptional repression
in cancer - local hypermethylation - TSGs maybe turned off
global hypomethylation - loss of methylation such as repetitive sequence and allows chromosomal instability

Question 20

Histone modifications

Answer 20

acetylated
phosphorylated
methylated

affects dna compactment
global changes in this - level of modifiers, modification profiles
modifiers can be mutated in cancer
HDAC inhibitors as therapy