Title |
Cancer Risk and the ATM Gene: a Continuing Debate
|
---|---|
Published in |
JNCI: Journal of the National Cancer Institute, May 2000
|
DOI | 10.1093/jnci/92.10.795 |
Pubmed ID | |
Authors |
Kum Kum Khanna |
Abstract |
Deficiencies in the ability of cells to sense and repair damage in individuals with rare genetic instability syndromes increase the risk of developing cancer. Ataxia-telangiectasia (A-T), such a condition, is associated with a high incidence of leukemia and lymphoma that develop in childhood. Although A-T is an autosomal recessive disorder, some penetrance appears in individuals with one mutated ATM gene (A-T carriers), namely, an increased risk of developing breast cancer. The gene mutated in A-T, designated ATM, is homologous to several DNA damage recognition and cell cycle checkpoint control genes from other organisms. Recent studies suggest that ATM is activated primarily in response to double-strand breaks, the major cytotoxic lesion caused by ionizing radiation, and can directly bind to and phosphorylate c-Abl, p53, and replication protein A (RPA). Analysis of ATM mutations in patients with A-T or with sporadic non-A-T cancers has suggested the existence of two classes of ATM mutation: null mutations leading to A-T and dominant negative missense mutations predisposing to cancer in the heterozygous state. Studies with A-T mouse models have helped determine the basis of lymphoid tumorigenesis in A-T and have shown that ATM plays a critical role in maintaining genetic stability by ensuring high-fidelity execution of chromosomal events. Thus, ATM appears to act as a caretaker of the genome. |
Mendeley readers
Geographical breakdown
Country | Count | As % |
---|---|---|
United Kingdom | 1 | 2% |
Unknown | 60 | 98% |
Demographic breakdown
Readers by professional status | Count | As % |
---|---|---|
Student > Ph. D. Student | 13 | 21% |
Student > Bachelor | 12 | 20% |
Student > Postgraduate | 7 | 11% |
Researcher | 4 | 7% |
Professor > Associate Professor | 4 | 7% |
Other | 7 | 11% |
Unknown | 14 | 23% |
Readers by discipline | Count | As % |
---|---|---|
Biochemistry, Genetics and Molecular Biology | 16 | 26% |
Agricultural and Biological Sciences | 14 | 23% |
Medicine and Dentistry | 10 | 16% |
Engineering | 3 | 5% |
Chemistry | 3 | 5% |
Other | 2 | 3% |
Unknown | 13 | 21% |