"At the time, people believed the mammalian genome was inviolate and didn't change at all," recalls Alt, who is also the Charles A. Janeway Professor of Pediatrics at Children's and a professor of Genetics at Harvard Medical School. "This discovery showed that cancer cells, at least, could change their genome drastically, and was the first clear-cut molecular demonstration of genomic instability in cancer."
N-myc oncogene amplification
The gene amplification work led Alt to co-discover a specific cancer-causing gene, or oncogene, known as N-myc. He found that N-myc is frequently amplified in neuroblastoma, a childhood brain cancer, making the cancer especially aggressive. "N-myc opened up oncogene amplification as important in cancer prognosis and in mechanisms of cancer progression," he notes. Oncogene amplification has since been found to be fundamental in many advanced-stage cancers, but Alt's N-myc discovery in the early 80s provided one of the first systematic associations with a particular tumor.
The non-homologous DNA end-joining pathway
During the 1980s, Alt also turned his attention to immunology studies, examining how the immune system can recognize and defend against an almost infinite variety of attackers. Serendipitously, this work also led to key discoveries about genomic instability.
The immune cells known as T lymphocytes have receptors that can recognize far more foreign invaders than the genome could possibly anticipate and encode for. The same is true of B lymphocytes, which can make a seemingly limitless variety of antibodies. The genes for these receptors and antibodies come in segments known as Vs, Ds, and Js. In co
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Contact: Susan Craig
susan.craig@childrens.harvard.edu
617-355-6420
Children's Hospital Boston
24-Mar-2004