5.4 Familial Cancer

Question 1

What are the types of mutations that can arise to cause cancer?

Answer 1

Acquired - somatic

Inherited - Germline

Question 2

What are the genes usually involved in cancer?

Answer 2

Mutated or activated oncogenes
Loss or mutated tumour suppressor genes
DNA repair genes

Question 3

How do oncogenes cause cancer?

Answer 3

1 mutation which causes accelerated cell division

Question 4

What is the oncogene over expressed in colon cancer?

Answer 4

RAS and C-MYC

Question 5

What is the oncogene over expressed in hereditary papillary renal cancer?

Answer 5

MET

Question 6

What is the oncogene over expressed in familial melanoma cancer?

Answer 6

CDK4

Question 7

What is the oncogene over expressed in CML cancer?

Answer 7

BCL/ABL

Question 8

What is the two hit hypothesis?

Answer 8

1 mutation causes the carrier to be susceptible and the 2nd mutation or loss causes cancer

Question 9

What type of gene is associated with familial cancer syndrome?

Answer 9

Tumour suppressor genes

Question 10

What are the clinical features suggestive of familial/inherited susceptibility?

Answer 10

Occurs at young age
Multiple tumours in single organ or bilateral paired
More than 1 primary
Family history or same type or related type
High rate in family

Question 11

What is the gene associated with retinoblastoma?

Answer 11

RB1 gene on chromosome 13

Question 12

What are the features of retinoblastoma?

Answer 12

Unilateral until 26 months, bilateral 8 months

Familial likely to be bilateral younger

Question 13

What type of genes are BRCA 1 and 2 and what is their inheritance)

Answer 13

Tumour suppressor genes (autosomal dominant)

Question 14

Where are BRCA 1 and 2 located?

Answer 14

1: chromosome 17
2: chromosome 13

Question 15

How do tumours in BRCA 1 and 2 carriers occur?

Answer 15

Need to have inactivation of both alleles, one inactivated as a result of inherited germline mutation and the second is acquired (somatic inactivation)

Question 16

What are the pathologic features of BRCA 1 and 2 breast cancer?

Answer 16

1: triple negative, high grade occurring in young women
2: ER+ and may occur late

Question 17

What are the management options for BRCA carriers?

Answer 17

Cancer screening
Prophylactic mastectomy
Prophylactic salpingo-oophrectomy

Question 18

Which gene is associated with increase risk of Male breast cancer?

Answer 18

BRCA2

Question 19

What is category 1 gene mutations and give examples

Answer 19

Highly penetrant genes with will recognised syndromes

BRCA 1/2, p53, CDH1, STK11, MMR

Question 20

What needs to be considered with genetic screening?

Answer 20

Need to give counselling and it is hard to know what to do with category 2/3 results

Question 21

What is TP53 mutation associated with?

Answer 21

Li-Fraumeni

Question 22

What is PTEN mutation associated with?

Answer 22

Cowden/PTEN hamartoma

Question 23

What is STK11 mutation associated with?

Answer 23

Peutz-Jeghers

Question 24

What is MMR gene mutations associated with?

Answer 24

Lynch (HNPCC)

Question 25

What is the difference between tumour suppressor genes and DNA repair genes?

Answer 25

TSG are directly involved in growth inhibition or differentiation while DNA repair genes are indirectly involved

Question 26

What usually occurs as a result of inactivation of DNA repair genes?

Answer 26

Increased rates of mutation in other cellular genes including proto-oncogenes and tumour suppressor genes

Question 27

What are the examples of DNA repair genes?

Answer 27

Neucleotide excision repair, mismatch repair and somatic mutational disorders

Question 28

How does Neuleotide excision repair work and what disorder results from muatation?

Answer 28

repairs helix-istorting chemical adducts especially UV light Xeroderma Pigmentosa

Question 29

What results from germline mutations in MMR genes and what are the genes?

Answer 29

HNPCC (Lynch syndrome) - typically right sided/proximal colon cancer MSH2, MLH1, MSH6 (PMS1, PMS2)

Question 30

What other cancers are associated with the MMR germline mutations?

Answer 30

Colorectal, Endometrial, Gastric, Ovarian, Biliary tract, Urinary tract, Small bowel, Brain/CNS

Question 31

What are the two (3) most common genes that are lost in HNPCC?

Answer 31

MSH2 and MSH6 the most common | MHL1 can also occur in sporadic CRC