Mechanisms of Functional Tumor Suppressor Loss

There are three main ways in which a cell can lose the functionality of its tumor suppressor genes. Chromosomal aberrations, such as balanced reciprocal translocations, can occur. In such translocations, two unlike chromosomes switch segments. The most common such aberration is the chromosome 11 and 22 t(11;22) (q23;q11) translocation. It occurs in 10 to 15 of every 10,000 newborns and is the most common cause of childhood leukemia. The chromosome 9 and 22 t(9;22)(q34;q11) translocation gives rise to the characteristic derivative of chromosome 22, called the Philadelphia chromosome after the city where it was first found, and results in chronic myelogenous leukemia.

Constitutional chromosomal aberrations, which include deletions and aneuploidy, are sometimes associated with an increase in specific kinds of cancers. For example, a deletion on chromosome 13 band q14.1 is associated with retinoblastoma. Trisomy 21 in individuals with Down syndrome is associated with a 1 percent occurrence of leukemia.

Viral oncoproteins can interact with tumor suppressor gene proteins. The human papillomavirus (HPV) is a small DNA virus that causes warts. Various subtypes of HPV are associated with cervical cancer. The viral transforming protein E7 has the ability to interact with the retinoblastoma protein, thus interfering with the cell cycle checkpoint controlled by the retinoblastoma protein. Similarly, another HPV gene, E6, interacts with the p53 gene, causing the degradation of the p53 protein, thus allowing the cell cycle to go unchecked. see also Apoptosis; Breast Cancer; Cancer; Cell Cycle; Chromosomal Aberrations; Colon Cancer; Oncogenes.

Giles Watts aneuploidy abnormal chromosome numbers

Bibliography

Rosenberg, S. A., and B. M. John. The Transformed Cell: Unlocking the Mysteries of Cancer. New York: Putnam, 1992.

Weinberg, R. A. Racing to the Beginning of the Road: The Search for the Origin of Cancer. New York: W. H. Freeman, 1998.

-. One Renegade Cell: How Cancer Begins. New York: Basic Books, 1999.

Twins

Twins are siblings carried together in the womb and born at the same time. Similarities and differences between twins can be used to answer questions about the role genes and the environment play in the development of traits such as personality, intelligence, and susceptibility to disease. While results from any single pair of twins cannot provide conclusive answers to such questions, the study of large numbers of twin pairs allows researchers to draw conclusions about inheritance with a significant degree of confidence.

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