of CancerKailin Yang and Jennifer S. Yu

BIOLOGY OF CANCER

KAILIN YANG AND JENNIFER S. YU

Question 1

What is a hallmark of cancer cells?

Question 2

What is a proto-oncogene?

Question 3

What is a tumor suppressor gene?

Question 4

What is a DNA stability gene?

Question 1 What is a hallmark of cancer cells?

Answer 1

The hallmark of cancer cells is deregulated control of cell division and failure for self-elimination. It is like a Darwinian-like process in which the fittest cells replicate to become the dominant population of a tumor.

Hall EJ, Giaccia AJ. Cancer biology. In: Hall EJ, Giaccia AJ, eds. Radiobiology for the Radiologists. 7th ed. Philadelphia, PA: Lippincott Williams & Wilkins; 2012:274–303.

Question 2 What is a proto-oncogene?

Answer 2

A proto-oncogene is a component of signaling networks that positively regulates cellular growth in response to mitogens, cytokines, and cell-to-cell contact. Gain-of-function mutation in only one copy of a proto-oncogene is sufficient to produce an active oncogene in a dominant manner that often fails to be regulated by extracellular signals.

Hall EJ, Giaccia AJ. Cancer biology. In: Hall EJ, Giaccia AJ, eds. Radiobiology for the Radiologists. 7th ed. Philadelphia, PA: Lippincott Williams & Wilkins; 2012:274–303.

Question 3 What is a tumor suppressor gene?

Answer 3

A tumor suppressor gene is a negative growth regulator. It modulates cellular proliferation and survival by antagonizing the functions of proto-oncogenes or responding to unchecked growth signals. In most cases, loss-of-function mutations of both copies of tumor suppressor are needed for tumor progression.

Hall EJ, Giaccia AJ. Cancer biology. In: Hall EJ, Giaccia AJ, eds. Radiobiology for the Radiologists. 7th ed. Philadelphia, PA: Lippincott Williams & Wilkins; 2012:274–303.

Question 4 What is a DNA stability gene?

Answer 4

DNA stability genes are a group of genes involved in monitoring and maintaining genomic integrity. Loss of DNA stability genes causes defects in proper sensing of DNA lesions and error-prone repair of a damaged DNA template.

Hall EJ, Giaccia AJ. Cancer biology. In: Hall EJ, Giaccia AJ, eds. Radiobiology for the Radiologists. 7th ed. Philadelphia, PA: Lippincott Williams & Wilkins; 2012:274–303.

Question 5

What causes normal tissues to transform into tumors and metastasize?

Question 6

What are the steps of malignant progression?

Question 7

Are tumors composed of a homogenous or heterogeneous group of neoplastic cells?

Question 8

In classic experiments performed in the 1970s, why could Rous sarcoma virus (RSV), but not the similar avian leukosis virus (ALV), cause cellular transformation and induce sarcoma?

Question 5 What causes normal tissues to transform into tumors and metastasize?

Answer 5

Malignant progression occurs in a series of steps over a period of time. Malignant progression is typically caused by gain-of-function mutations that activate oncogenes, loss-of-function mutations that inactivate tumor suppressor genes, and loss of activity of DNA stability genes that increases the probability of genomic instability. These gene changes result from random errors or exposure to various agents including chemical mutagen, ionizing radiation, ultraviolet light, and viral infection. Malignant progression gradually alters the regulatory mechanisms of a single cell in proliferation, self-elimination, immortalization, and genetic stability, creating the clonal origin of a tumor. Tumors also evade immune mechanisms.

Hall EJ, Giaccia AJ. Cancer biology. In: Hall EJ, Giaccia AJ, eds. Radiobiology for the Radiologists. 7th ed. Philadelphia, PA: Lippincott Williams & Wilkins; 2012:274–303.

Question 6 What are the steps of malignant progression?

Answer 6

Cancers seem to develop progressively. Between the two extremes of fully normal and highly metastatic tissues, there are a spectrum of steps, including hyperplasia, metaplasia, dysplasia, and neoplasia.

Weinberg RA. The Biology of Cancer. New York, NY: Garland Science; 2007.

Question 7 Are tumors composed of a homogenous or heterogeneous group of neoplastic cells?

Answer 7

Although tumor cells are considered clonal in origin, most tumor types contain heterogeneous populations of cells that differ in their ability to repopulate the tumor or form metastases. In many cancers, only a small percentage of tumor cells possess the ability to form a tumor, leading to the concept that tumors possess “stem-like cells” and that elimination of these stem-like cells is essential for controlling tumor growth.

Hall EJ, Giaccia AJ. Cancer biology. In: Hall EJ, Giaccia AJ, eds. Radiobiology for the Radiologists. 7th ed. Philadelphia, PA: Lippincott Williams & Wilkins; 2012:274–303.

Question 8 In classic experiments performed in the 1970s, why could Rous sarcoma virus (RSV), but not the similar avian leukosis virus (ALV), cause cellular transformation and induce sarcoma?

Answer 8

RSV, an RNA retrovirus, contains approximately 1,500 more base pairs (bp) of sequence than ALV. This unique piece of sequence was later found to contain genetic information to encode the v-src gene, which drives cellular transformation. The v-src gene is the malignant form of the cellular proto-oncogene c-src.

Hall EJ, Giaccia AJ. Cancer biology. In: Hall EJ, Giaccia AJ, eds. Radiobiology for the Radiologists. 7th ed. Philadelphia, PA: Lippincott Williams & Wilkins; 2012:274–303.

Question 9

What are four mechanisms for oncogene activation in human neoplasms?

Question 10

What is the Philadelphia chromosome seen in chronic myeloid leukemia (CML) patients?

Question 11

Which gene is mutated in familial retinoblastoma (Rb)? What is the epidemiological inheritance pattern of this mutation?

Question 12

What is the key paradigm shift in the “two-hit hypothesis” proposed by Knudson?

Question 9 What are four mechanisms for oncogene activation in human neoplasms?

Answer 9

Four mechanisms are retroviral integration through recombination, DNA mutation of regulatory sites, gene amplification, and chromosome translocation.

Hall EJ, Giaccia AJ. Cancer biology. In: Hall EJ, Giaccia AJ, eds. Radiobiology for the Radiologists. 7th ed. Philadelphia, PA: Lippincott Williams & Wilkins; 2012:274–303.

Question 10 What is the Philadelphia chromosome seen in chronic myeloid leukemia (CML) patients?

Answer 10

The Philadelphia chromosome, the shortened version of chromosome 22, is caused by symmetric translocation between chromosomes 9 and 22 that creates a novel fusion transcript encoding bcr-abl whose aberrant expression drives the development of CML.

Hall EJ, Giaccia AJ. Cancer biology. In: Hall EJ, Giaccia AJ, eds. Radiobiology for the Radiologists. 7th ed. Philadelphia, PA: Lippincott Williams & Wilkins; 2012:274–303.

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