Cancer Genetics Flashcards
What are the 3 ways cancer develops?
- Spontaneous Mutation/Defect in DNA replication.
- Induced mutations from environmental agents (Carcinogens)
- Inherited mutations
What is the function of Proto-oncogenes.
Maintain ordered progression through cell cycle, division and differentiation. (Growth factors/receptors, Signal transducers, Transcription factors)
What is an oncogene? Describe it.
A mutated proto-oncogene. Increased expression of proto-oncogene. A change in structure/function of proto-oncogene.
What does an oncogene lead to?
Increased cell division and proliferation.
Describe oncogene behavior at the cellular level.
Acts as a dominant disease gene. You only need one mutated allele to get it.
Describe Multiple Endocrine Neoplasia (MEN2)
95-100% risk medullary thyroid carcinoma.
- MEN2A; MEN2B for infants.
- Prophylactic thyroidectomy recommended
What are other features of the RET proto-oncogene?
Parathyroid adenoma/hyperplasia, mucosal neuromas of lips and tongue
Describe the affects of a somatic chromosomal rearrangement.
If the rearrangement affects a proto-oncogene ( or tumor suppressor gene), it can lead to cancer. These are sporadic cancers, NOT INHERITED.
Describe the Philadelphia Chromosome.
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.
What is the function of a tumor-suppressor gene?
Acts as a checkpoint to help control cell division and suppress inappropriate cell proliferation.
What are the two types of Tumor-suppressor genes?
Gatekeepers and Caretakers
What do gatekeepers do?
Directly involved in cell cycle regulation. Role in growth inhibition and apoptosis. Mutations result in lack of growth inhibition.
What to caretakers do?
They are DNA repair genes. Mutations lead to cancer INDIRECTLY by allowing other mutations to accumulate. Mutations are inherited as autosomal dominant.
Describe the behavior of tumor-suppressor genes at the cellular level.
Act recessive; A mutation in both alleles is required for impact.
Explain the two-hit hypothesis for sporatic cancer.
Since tumor-suppressor genes act in a recessive manor, you need TWO mutant alleles to develop a cancer cell.
Explain the two-hit hypothesis for hereditary cancer.
One mutation is already inherited and is within every cell. A second hit in any cell will cause cancer. Ex: Hereditary Retinoblastoma
What are the features of hereditary cancers?
Earlier age of onset, Increased risk of getting a second ‘hit’, and multifocal presentations.
What two genes account for 85% of hereditary breast/ovarian cancer families?
BRCA1 and BRCA2
Which genes are involved in DNA repair?
Caretaker genes; They respond to double stranded DNA breaks.
What are key features of BRCA1/2 families?
Early onset breast cancer, Bilateral breast cancer, Breast and ovarian cancer in the same person/family, and Male breast cancer.
How much of colon cancer is hereditary?
5-10%
Describe Familial Adenomatous Polyposis. (FAP)
Characterized by hundreds to thousands of polyps lining the colon and rectum. Average age of onset is 16. CHRPE spots in eye, and osteomas.
Does a negative test rule out hereditary cancer? How are the tested for?
NO; DNA sequencing
