Lecture 34

Question 1

There are three main genetic alterations associated with the progression of cancer.

1. Activation of ___-______
2. Loss of ____ ____ genes
3. Loss of _______ instability genes (this increases mutation frequency.)

Answer 1

Proto-oncogenes

Tumor Suppressor genes

Chromosomal instability genes

Question 2

Activation of Proto-oncogenes is typically ___-of-function and can result in a ______ change (increased production of an unaltered gene product) or ______ change (production of modified gene product).

Answer 2

Quantitative

Qualitative

Question 3

There are 3 mechs by which proto-oncogenes can become oncogenes.

1. ____ mutation
2. Gene ______
3. ______

Answer 3

1. Point Mutation
2. Gene rearrangement
3. Amplification

Question 4

A _____ mutation in position 12 of the Ras protein, for example, knocks out its intrinsic hydrolysis activity –> it remains bound to GTP and thus constitutively active.

Answer 4

Point Mutation

Question 5

The _____ chromosome that results from rearrangement of chromosomes 9 and 22 is an example of rearrangement leading to oncogene formation. It is important to note this rearrangement does NOT disrupt the ______ frame of either the BCR or ABL genes that are combined. The resultant fusion gene generates a fusion protein that acts as a constitutively active _____ kinase. Normally, ABL acts in the nucleus to induce apop.

Answer 5

Philadelphia Chromosome

Reading frame

Tyrosine kinase

Question 6

Follicular lymphoma is caused by a gene rearrangement leading to formation of an oncogene. Chromosomes ___ and ___ are involved in more that 85% of cases, and it occurs in B-cells. The result of the translocation constitutively activates ____ (antiapoptotic gene).

Answer 6

14 and 18

Bcl2

Question 7

Gene amplification can occur in two ways. One way exhibits a ______ staining region on a chromosome, representing an area that was amplified. The other is called Double _____, and these form when pieces of DNA break off and circularize. If a proto-oncogene is involved in either of these two, amplification of the gene can lead to oncogenesis.

Answer 7

Homogenous Staining Region

Double Minutes

Question 8

____2 is an EGF receptor in breast cancer. Normally, there is not much ligand, so with the normal amount of receptors, there’s no response. However, in breast cancer, the receptor is amplified and covers the surface of the cells, thus it can respond to EGF at very low concentrations.

Answer 8

HER2

Question 9

Telomerase activity is another hallmark of cancer cells. ______ is the gene that is amplified and/or overexpressed bc of promoter mutations or rearrangements.

Answer 9

hTERT

Question 10

Unlike protooncogenes for which only one copy of the gene needs to be altered to induce oncogenesis, both copies of _____ suppressor genes must be inactivated to observe a phenotype.

Answer 10

Tumor Suppressor genes

Question 11

Rb is a tumor suppressor gene implicated in Familial and Sporadic retinoblastoma. In Familial, it results from a highly penetrant autosomal _____ mutation. In this case, patients present with multiple tumors in both eyes, and non-ocular tumors increase with ____.

How does this differ from Sporadic Rb?

Answer 11

Dominant

Age

Sporadic presents as a single tumor in one eye and no secondary non-ocular tumors.