Deck 22: Cancer Genetics

Question 1

Cancer is fundamentally a genetic disease. Mutations in several genes are usually required to produce cancer. If one of these mutations is inherited, fewer somatic mutations are necessary for cancer to develop, and the person may have a predisposition to cancer. Clonal evolution is the accumulation of mutations in a clone of cells.
-How does the multistep model of cancer explain the observation that sporadic cases of retinoblastoma usually appear in only one eye, whereas inherited forms of the cancer appear in both eyes?

Answer 1

Retinoblastoma results from at least two separate genetic defects, both of which are necessary for cancer to develop. In sporadic cases, two successive mutations must occur in a single cell, which is unlikely and therefore typically affects only one eye. In people who have inherited one of the two required mutations, every cell contains this mutation, and so a single additional mutation is all that is required for cancer to develop. Given the millions of cells in each eye, there is a high probability that the second mutation will occur in at least one cell of each eye, producing tumors in both eyes and the inheritance of this type of retinoblastoma.

Question 2

Proto-oncogenes are genes that control normal cellular functions. When mutated, proto-oncogenes become oncogenes that stimulate cell proliferation. They tend to be dominant in their action. Tumor-suppressor genes normally inhibit cell proliferation; when mutated, they allow cells to proliferate. Tumor-suppressor genes tend to be recessive in their action. Individual organisms that are heterozygous for tumor-suppressor genes are often predisposed to cancer.
-Why are oncogenes usually dominant in the their action, whereas tumor-suppressor genes are recessive?

Answer 2

Oncogenes have a stimulatory effect on cell proliferation. Mutations in oncogenes are usually dominant because a mutation in a single copy of the gene is usually sufficient to produce a stimulatory effect. Tumor-suppressor genes inhibit cell proliferation. Mutations in tumor-suppressor genes are generally recessive, because both copies must be mutated to remove all inhibition.

Question 3

Progression through the cell cycle is controlled at checkpoints, which are regulated by interactions between cyclins and cyclindependent kinases. Genes that control the cell cycle are frequently mutated in cancer cells.

-What would be the most likely effect of a mutation that causes cyclin B to be unable to bind to CDK?

A) Cells pass through the G2/M checkpoint and enter mitosis even when DNA has not been replicated.
B) Cells never pass through the G1/S checkpoint.
C) Cells pass through mitosis more quickly than unmutated cells.
D) Cells fail to pass the G2/M checkpoint and do not enter into mitosis

Answer 3

Cells fail to pass the G2/M checkpoint and do not enter into mitosis

Question 4

Molecules outside the cell often bring about intracellular responses by binding to a membrane receptor and stimulating a cascade of intracellular reactions, known as a signal-transduction pathway. Many molecules in the pathway are proteins that alternate between active and inactive forms. Defects in signal-transduction pathways are often associated with cancer.

-Ras proteins are activated when they

A) bind GTP.
B) release GTP.
C) bind GDP.
D) undergo acetylation.

Question 5

Mutations in genes that encode components of DNA-repair systems are often associated with cancer; these mutations increase the rate at which mutations are retained and result in an increased number of mutations in proto-oncogenes, tumor-suppressor genes, and other genes that contribute to cell proliferation. Mutations that allow telomerase to be expressed in somatic cells and those that affect vascularization and metastasis also may contribute to cancer progression.

-Which type of mutation in telomerase could be associated with cancer cells?

A) Mutations that produce an inactive form of telomerase
B) Mutations that decrease the expression of telomerase
C) Mutations that increase the expression of telomerase
D) All of the above

Question 6

Many tumors contain a variety of types of chromosome mutations. Some tumors are associated with specific deletions, inversions, and translocations. Deletions can eliminate or inactivate genes that control the cell cycle; inversions and translocations can cause breaks in genes that suppress tumors, fuse genes to produce cancer-causing proteins, or move genes to new locations, where they are under the influence of different regulatory sequences.

-Chronic myelogenous leukemia is usually associated with which type of chromosome rearrangement?

A) Duplication
B) Deletion
C) Inversion
D) Translocation

Question 7

Changes in patterns of methylation of DNA are often associated with cancer. Changes in DNA methylation potentially affect the expression of tumor-suppressor genes and may contribute to chromosome instability.

-Hypermethylation is thought to contribute to cancer by

A) inhibiting DNA replication.
B) inhibiting the expression of tumor-suppressor genes.
C) stimulating the translation of ongenes.
D) stimulating telomerase.