genetics and cancer

Question 1

what do cells acquire as they divide

Answer 1

mutations

Question 2

what exists to attempt to fix these mutations

Answer 2

repair mechanisms

Question 3

what is cancer a disease of

Answer 3

mosaicism largely caused by post-zygotic mutation

gamete → zygote → embryo → human

• Heterogenous

Question 4

what are driver mutations

Answer 4

Mutations that drive cancer

Question 5

what are the 2 classes of driver mutations

Answer 5

oncogenes and tumour suppressors

Question 6

what is a passenger mutation

Answer 6

incidental mutations that happen because the tumour is unstable

Question 7

what is epigeneics

Answer 7

The study of changes in gene expression without a change in DNA sequence
- DNA methylation
- Interaction with histone proteins

Question 8

what does methylation do

Answer 8

switches gene off

Question 9

where does DNA methylation occur

Answer 9

on cytosine bases before guanine bases

Question 10

what is DNA methylene regarding repair genes

Answer 10

it is deficient DNA repair genes or tumour suppressor genes due to hypermethylation = cancer

Question 11

what does methylation increase

Answer 11

mutation

Question 12

describe retinoblastoma

Answer 12

autosomal dominant

Variable penetrance - not everyone with mutation has disease

Question 13

what is retinoblastoma

Answer 13

a tumour suppressor gene

• Need to lose two copies for tumour to develop
• Both copies can be lost by somatic mutation

Question 14

what are the methods of gene activation

Answer 14

Duplication of the gene

Activation of the gene promoter

Change in amino acid sequence – active protein configuration

Question 15

what does activating mutation in BRAF activate

Answer 15

the KRAS pathway

Question 16

Due to genetic mutation, cancer cells may:

Answer 16

1. Produce their own extracellular growth factors
2. Overexpress growth factor receptors
3. Have active proteins that do not require phosphorylation

Question 17

how would you activate oncogenes

Answer 17

Activated from proto-oncogenes due to dominant gain of function mutations:

Question 18

BRAF:

Answer 18

codes for a Raf Kinase protein involved in MAP-K signal pathway

Question 19

why is the signal always on in point mutation

Answer 19

Point mutation removes the need for phosphorylation - signal is always on

Question 20

Vemurafenib

Answer 20

BRAF inhibitor HOWEVER easily overcome due to multiple activation pathways for Raf kinase

Question 21

HER2 in breast cancer:

Answer 21

• amplification results in too many HER2 receptors → increased signal for proliferation
  
  • Trastuzumab binds to HER2 receptors, blocking proliferation signal

Question 23

Philadelphia chromosome:

Answer 23

translocation which produces a hyperactive fusion protein (BCR-ABL)

Question 24

what is a tumour suppressors

Answer 24

Genes whose loss (deletions, point mutations) results in carcinogenesis

Question 25

Retinoblastoma

Answer 25

• pRB - functions at G1 checkpoint
• Mutation in RB gene → loss of function of pRB → retinoblastoma

Question 26

Two-hit hypothesis

Answer 26

• Mutation of both alleles necessary to inactivate tumour suppressor genes
• The reason cancers are often associated with old age - mutation rates are slow so over a longer time, increased chance of two ‘hits’

Question 27

Oncogenic signature

Answer 27

• Characteristic of a cancer is determined by its driver mutations
• Cancer cells easily mutate, so quicker evolution of cancer cells

Question 28

Mismatch repair comple - Lynch syndrome:

Answer 28

hereditary form of cancer due to mutation in mismatch repair gene

Question 29

Cancer risk

Answer 29

Multifactorial - rarely purely genetic

Question 30

Features which indicate inherited cancer susceptibility

Answer 30

• Several first/second degree relatives with cancer
• Several close relatives with related cancers
• Unusually early onset
• Bilateral tumours in paired organs
• Tumours in two organ systems in one individual