Lecture 6a: Defects in Tumor Suppressor Genes

Question 1

Tumor supressor genes

Answer 1

Encodes a protein that regulates cell division.

Question 2

Cancer-susceptibility gene

Answer 2

A gene, when changed, gives an individual an increased risk for developing cancer.

Question 3

Tumors suppressors can act as ________

Answer 3

1. Gatekeepers: Check progression through the cell cycle and division
2. Caretakers: Maintenance of cellular genome.

Question 4

5 types of functionality of tumor suppressor genes

Answer 4

1. Cell cycle progression
2. Receptors or signal transducers
3. Checkpoint-control proteins
4. Induction of apoptosis
5. Repair of DNA

Question 5

Biologic functions of tumor suppressor genes

Answer 5

1. Inhibition of mitogenic signaling pathways
2. Inhibition of cell cycle progression
3. Inhibition of “pro-growth” programs of metabolism and angiogenesis
4. Inhibition of invasion and metastasis
5. Maintain chromosomal stability
6. DNA repair factors
7. Induction of apoptosis

Question 6

Hereditary cancers

Answer 6

Cancers caused by germline mutations (5-10%)

Question 7

Somatic/Acquired cancers

Answer 7

Cancers occuring from damage to genes in an individual cell during a persons life time.

Question 8

Predisposition

Answer 8

Type of inherited disorder in which there is a higher-than-normal risk of certain types of cancer

Question 9

Cowden syndrome

Answer 9

Rare inherited disorder marked by the presence of many benign growths called hamartomas and an increased risk of developing cancerous tumors of the breast, thyroid, endometrium, colorectal, kidney, and skin. Caused by mutations in PTEN gene.

Question 10

Neurofibromatosis Type 1 (NF1)

Answer 10

Genetic condition that causes tumors to grow along the nerves. Tumors are usually non-cancerous but eventually become cancerous.

Question 11

Retinoblastoma

Answer 11

RB gene “Governor of the cell cycle,” encodes the RB protein that inhibits E2F transcription factors. These transcription factors regulate genes that are essential for cells to pass from G1 to S phase.

Question 12

Loss of function mutation and inhibition of RB consequences

Answer 12

When oncoproteins bind, it can inhibit the antiproliferative effect of RB in cancers

Question 13

Pediatric retinoblastomas

Answer 13

-Tumors arise from precursor cone cells.
-Often presents as a an opacity that obscures the retina.
-Inherited condition caused by inactivating mutation in the RB1 gene that causes a 10,000 fold increase of retinoblastoma as compared to the general population

Question 14

Leukocoria

Answer 14

“White pupil” refers to the of white light seen upon direct illumination of the fundus through the pupil. Compared to red glow

Question 15

Two hit hypothesis

Answer 15

Tumor suppressor genes can undergo a variety of mutations; however, most loss of function mutations that occur in tumor suppressor genes are recessive in nature. Thus, in order for a cell to become cancerous, both of the cells tumor suppressor genes must be mutated.

Question 16

Knudson’s 2-hit hypothesis (Inherited forms)

Answer 16

In the inherited form of retinoblastoma children inherit 1 mutated RB allele and the other copy is normal. Retinoblastoma develops when the normal retinoblastoma (RB) allele undergoes a spontaneous somatic mutation. The second mutation is the “Second it”

Question 17

Knudson’s 2-hit hypothesis in sporadic cases of RB

Answer 17

Both normal RB alleles undergo a somatic mutation in the same cell. The probability is low which explains why retinoblastoma is so uncommon.

Question 18

Loss of heterozygosity

Answer 18

Loss of one parent’s contribution to the cell. When loss of heterozygosity involves the normal allele, it creates a cel that is more likely to show malignant growth if the altered gene is a tumor suppressor gene.

Question 19

Costello Syndrome

Answer 19

Causes distinct facial characteristics and symptoms due to cells growing and dividing too often.