Lecture 33: Genes and cancer part 2

Question 1

Whats a strong indicator of familial cancer?

Answer 1

• Young age onset

- Often multiple types in family

Question 2

Whats the genetic mutation basis of cancer?

Answer 2

• Oncogenes
• Tumour suppressor genes
• Apoptotic genes
• DNA repair genes

Question 3

Whats an oncogene that might be common in familial cancers?

Answer 3

RET oncogene (Rearranged during transfection)

• Receptor tyrosine kinase
• Germline mutations associated with MEN type 2 and familial medullary thyroid cancer

Uncommon because likely to be the lethal germline mutation

Question 4

What are some examples of inherited cancer?

Answer 4

Breast, ovary = BRCA1 and 2

Colorectal cancer = hMLH1, hMSH2

Question 5

What are the types of familial bowel cancer?

Answer 5

HNPCC

Familial adenomatous polyposis

Question 6

What is the genetic basis of HNPCC?

Answer 6

Heterozygous for germline )inherited) mutation in DNA mismatch repair genes

i.e hMSH2, hMLH1

Question 7

Whats the implications of the defective mismatch repair genes in NHPCC?

Answer 7

• Inactivation of both alleles increases mutation rate - in microsatellite regions
• Alters a number of cell regulatory genes - increased risk of cancer
• Microsatellite instability seen in the cancer i.e Marker of mistmatch repair gene defect

Question 8

What is increasing microsatellite instability associated with?

Answer 8

Cancer formation

Question 9

What does the genetics of HNPCC lead to?

Answer 9

Develops guidelines for screening frequency etc.

• How many microsatellite regions are there
• What genes have they got etc

Question 10

What genes have been identified in FAP?

Answer 10

Linkage studies placed gene chromosome 5q -APC gene identified

Question 11

What is the APC gene in FAP?

Answer 11

Tumour suppressor gene

• Inherited germline mutation
• Most mutations frameshift or nonsense - yield truncated protein
• Second hit required, sometimes hypermethylation

Question 12

What is BRCA1 and 2 associated with?

Answer 12

75-85% have risk of breast cancer
45% risk for ovarian (BRCA-1)
30% risk for ovarian (BRCA-2)

Question 13

What does BRCA1 and 2 not being 100% risk mean?

Answer 13

The gene does not have full penetrance

Other risk modifying factors - environmental, hormonal, genetic

Question 14

What is the function of BRCA1,2 and what does the mutation result in?

Answer 14

Many mutations

Mutations usually result in truncated proteins that are involved in DNA repair

Question 15

What are the potential issues with genetic testing in cancer?

Answer 15

Potential for discrimination i.e insurance, employment
Stresses
Guilt if not affected
Guilt if affected and have kids.