Cancer Genetics

Question 1

What are the 3 ways cancer develops?

Answer 1

1. Spontaneous Mutation/Defect in DNA replication.
2. Induced mutations from environmental agents (Carcinogens)
3. Inherited mutations

Question 2

What is the function of Proto-oncogenes.

Answer 2

Maintain ordered progression through cell cycle, division and differentiation. (Growth factors/receptors, Signal transducers, Transcription factors)

Question 3

What is an oncogene? Describe it.

Answer 3

A mutated proto-oncogene. Increased expression of proto-oncogene. A change in structure/function of proto-oncogene.

Question 4

What does an oncogene lead to?

Answer 4

Increased cell division and proliferation.

Question 5

Describe oncogene behavior at the cellular level.

Answer 5

Acts as a dominant disease gene. You only need one mutated allele to get it.

Question 6

Describe Multiple Endocrine Neoplasia (MEN2)

Answer 6

95-100% risk medullary thyroid carcinoma.

• MEN2A; MEN2B for infants.
• Prophylactic thyroidectomy recommended

Question 7

What are other features of the RET proto-oncogene?

Answer 7

Parathyroid adenoma/hyperplasia, mucosal neuromas of lips and tongue

Question 8

Describe the affects of a somatic chromosomal rearrangement.

Answer 8

If the rearrangement affects a proto-oncogene ( or tumor suppressor gene), it can lead to cancer. These are sporadic cancers, NOT INHERITED.

Question 9

Describe the Philadelphia Chromosome.

Answer 9

Translocation involving chromosome 9 and 22. Breakpoints in the proto-oncogene ABL (ch9) and BCR (ch22) results in a fused gene that changes the function of the ABL gene. Leas to abnormal cell proliferation.

Question 10

What is the function of a tumor-suppressor gene?

Answer 10

Acts as a checkpoint to help control cell division and suppress inappropriate cell proliferation.

Question 11

What are the two types of Tumor-suppressor genes?

Answer 11

Gatekeepers and Caretakers

Question 12

What do gatekeepers do?

Answer 12

Directly involved in cell cycle regulation. Role in growth inhibition and apoptosis. Mutations result in lack of growth inhibition.

Question 13

What to caretakers do?

Answer 13

They are DNA repair genes. Mutations lead to cancer INDIRECTLY by allowing other mutations to accumulate. Mutations are inherited as autosomal dominant.

Question 14

Describe the behavior of tumor-suppressor genes at the cellular level.

Answer 14

Act recessive; A mutation in both alleles is required for impact.

Question 15

Explain the two-hit hypothesis for sporatic cancer.

Answer 15

Since tumor-suppressor genes act in a recessive manor, you need TWO mutant alleles to develop a cancer cell.

Question 16

Explain the two-hit hypothesis for hereditary cancer.

Answer 16

One mutation is already inherited and is within every cell. A second hit in any cell will cause cancer. Ex: Hereditary Retinoblastoma

Question 17

What are the features of hereditary cancers?

Answer 17

Earlier age of onset, Increased risk of getting a second ‘hit’, and multifocal presentations.

Question 18

What two genes account for 85% of hereditary breast/ovarian cancer families?

Answer 18

BRCA1 and BRCA2

Question 19

Which genes are involved in DNA repair?

Answer 19

Caretaker genes; They respond to double stranded DNA breaks.

Question 20

What are key features of BRCA1/2 families?

Answer 20

Early onset breast cancer, Bilateral breast cancer, Breast and ovarian cancer in the same person/family, and Male breast cancer.

Question 21

How much of colon cancer is hereditary?

Answer 21

5-10%

Question 22

Describe Familial Adenomatous Polyposis. (FAP)

Answer 22

Characterized by hundreds to thousands of polyps lining the colon and rectum. Average age of onset is 16. CHRPE spots in eye, and osteomas.

Question 23

Does a negative test rule out hereditary cancer? How are the tested for?

Answer 23

NO; DNA sequencing