How do we know that malignant tumors arise from a single cell that contains mutations?

How do we know that cancer development requires more than one mutation?

How do we know that cancer cells contain defects in DNA repair?

What is the relationship between signal transduction and cellular proliferation?

Where are the major regulatory points in the cell cycle?

List the functions of kinases and cyclins, and describe how they interact to cause cells to move through the cell cycle.

What is the difference between saying that cancer is inherited and saying that the predisposition to cancer is inherited?

What is apoptosis, and under what circumstances do cells undergo this process?

Define tumor-suppressor genes. Why is a mutated single copy of a tumor-suppressor gene expected to behave as a recessive gene?

How does the p53 tumor-suppressor protein control cell-cycle checkpoints?

If a cell suffers damage to its DNA while in S phase, how can this damage be repaired before the cell enters mitosis?

Distinguish between oncogenes and proto-oncogenes. In what ways can proto-oncogenes be converted to oncogenes?

Of the two classes of genes associated with cancer, tumor-suppressor genes and oncogenes, mutations in which group can be considered gain-of-function mutations? In which group are the loss-of-function mutations? Explain.

How do translocations such as the Philadelphia chromosome contribute to cancer?

How do normal cells protect themselves from accumulating mutations in genes that could lead to cancer? How do cancer cells differ from normal cells in these processes?

Radiotherapy (treatment with ionizing radiation) is one of the most effective current cancer treatments. It works by damaging DNA and other cellular components. In which ways could radiotherapy control or cure cancer, and why does radiotherapy often have significant side effects?

Genetic tests that detect mutations in the BRCA1 and BRCA2 tumor-suppressor genes are widely available. These tests reveal a number of mutations in these genes—mutations that have been linked to familial breast cancer. Assume that a young woman in a suspected breast cancer family takes the BRCA1 and BRCA2 genetic tests and receives negative results. That is, she does not test positive for the mutant alleles of BRCA1 or BRCA2. Can she consider herself free of risk for breast cancer?

What is the cancer stem cell hypothesis?

As part of a cancer research project, you have discovered a gene that is mutated in many metastatic tumors. After determining the DNA sequence of this gene, you compare the sequence with those of other genes in the human genome sequence database. Your gene appears to code for an amino acid sequence that resembles sequences found in some serine proteases. Conjecture how your new gene might contribute to the development of highly invasive cancers.

A study by Bose and colleagues (1998). Blood 92:3362-3367] and a previous study by Biernaux and others (1996). Bone Marrow Transplant 17:(Suppl. 3) S45–S47] showed that BCR-ABL fusion gene transcripts can be detected in 25 to 30 percent of healthy adults who do not develop chronic myelogenous leukemia (CML). Explain how these individuals can carry a fusion gene that is transcriptionally active and yet does not develop CML.

Those who inherit a mutant allele of the RB1 tumor-suppressor gene are at risk for developing a bone cancer called osteosarcoma. You suspect that in these cases, osteosarcoma requires a mutation in the second RB1 allele, and you have cultured some osteosarcoma cells and obtained a cDNA clone of a normal human RB1 gene. A colleague sends you a research paper revealing that a strain of cancer-prone mice develops malignant tumors when injected with osteosarcoma cells, and you obtain these mice. Using these three resources, what experiments would you perform to determine:

(a) Whether osteosarcoma cells carry two RB1 mutations

(b) Whether osteosarcoma cells produce any pRB protein

(c) If the addition of a normal RB1 gene will change the cancer-causing potential of osteosarcoma cells?