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Combined physical and genetic map finds cancer's 'ignition key'
Date:5/5/2008

James M. Crawford, M.D., Ph.D., professor and chair of the University of Florida College of Medicine Department of Pathology, Immunology and Laboratory Medicine. Devoting that much space to a single paper is highly unusual, but Crawford is convinced its worthwhile. A person should be able to read this paper and know this entire, important story, Crawford said.

The paper documents three waves of genetic hits, mainly involving genetic deletions, that drive cells from normal to precancerous states. The first wave leads to widespread expansion of urothelial cells that harbor genetic changes but otherwise appear normal under microscopic analysis.

The second wave provides a growth advantage to cells that now have recognizable outward features of dysplasia precancerous cellular abnormalities. The third wave fully transforms the cells appearance and features the onset of severe dysplasia or carcinoma in situ, noninvasive cancer still limited to its tissue of origin, in this case the urothelium. Carcinoma in situ and dysplasia advance to invasive cancer.

The team mapped the tissue of five cancerous bladders. Next, they employed 787 DNA markers to identify chromosomal regions that display genetic deletions. By superimposing the low-resolution map of genetic variation over the geographic map of the organs tissue, they identified regions associated with both first-wave and second-wave cells.

Additional analysis narrowed the chromosomal regions to portions of six chromosomes. These six sites were confirmed by testing multiple markers of genetic loss in those chromosomal regions in the urine and blood of 32 bladder cancer patients and 31 disease-free patients with a history of bladder cancer. Genetic losses from at least one of the six regions were found in 98 percent of patients. In 82 percent of the cases, two to five chromosomal regions were involved.

Silenced forerunners stifle a tumor-suppressor

The team chose the 13q14 r
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Contact: Scott Merville
smerville@mdanderson.org
713-792-0661
University of Texas M. D. Anderson Cancer Center
Source:Eurekalert

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