Genetics of cancer

Question 1

What is the ‘two-hit’ hypothesis (Knudson)

Answer 1

Paticular reference to retinoblastoma - some occured early in infancy and some later.

Develop 1 mutation (somatic) then eventually a 2nd mutation= uncontrolled

If you already inherit one faulty copy but if a few cell divisions develop a 2nd mutation (hit) = triggers cancer

Question 2

Is cancer inherited?

Answer 2

Cancer is not inherited. it is the predisposition/tendency that’s inherited

Genetic changes occurring in somatic cells. Accumulating errors in the genome= lack of control of growth of tissues.

Question 3

What are proto-oncogenes.

Answer 3

Proto-oncogenes (acceleration)

Important in normal cell growth. when you have a mutation, there is a ‘gain of function’ and more activity of that gene. usually somatic mutations.

(stuck on accelerator)

Question 4

Tumor supressor genes

Answer 4

normal function is to suppress inappropriate cell proliferation

loss of function of ‘breaks’

both alleles must be hit (the second by a somatic hit)

recessive at cellular level

examples: retinoblastoma, BRCA1

(break is not working)

Question 5

Philadelphia Chromosome

Answer 5

Chronic myeloid leukaemia. fusion protein is created. Translocation of gene 9 and 22.

Question 6

What is methylation of DNA?

Answer 6

If DNA is methylated it’s inactive.

hypomethylation: If you under methylate the chromatin there is relative instability = oncogene activation

if a region is hypermethylated - switch of tumour surpressor gene activity = contributes to onset of cancer.

Question 7

Retinoblastoma

Answer 7

tumour in the back of eye
early on in infancy
child is blind (no red reflex= photographs)
screened by ophthalmologists

Question 8

Peutz-Jeghers syndrome

Answer 8

haematomas lesions on the lips
risk of intussusception
39% risk of colon cancer
mutation in STK11 gene

Question 9

Manchester scoring system

Answer 9

Number of cancers
Weighted for age diagnosis
Female breast cancer
Male breast cancer
Ovarian cancer
Prostate cancer
Pancreatic cancer

Question 10

BRCA1 mutation carriers

Answer 10

early breast surveillants mammography and MRI

Risk reducing surgery

Question 11

Hereditary colorectal cancer (CRC)

Answer 11

Lynch syndrome / Non polyposis colon cancer (HNPCC)

Familal adenomatous polyposis (FAP)

MYH associated polyposis (MAP)

Diffuse gastric cancer (e-cadherin)