In the first application of a newly developed technique, University ofCalifornia-San Francisco researchers found locations of previously unknowngenetic abnormalities in breast cancers, including three found in about15 percent of breast tumors.
The findings were reported in Tuesday's issue of the Proceedings of theNational Academy of Science. Research was led by Fred Waldman, associateprofessor of laboratory medicine at UCSF.
"The technique allows us to examine tumor DNA to look for chromosomealteration," Waldman told BioWorld. "It's allowing us to look for thesealterations with greater sensitivity than was previously possible. We'vefound a number of genetic changes in breast cancers that were notpreviously known."
The technique, called comparative genomic hybridization (CGH), does notneed probes to target specific DNA sequences or prior knowledge about locationsof abnormal DNA.
"We haven't found the genes at the sites of the chromosomal alterations,but we feel when we do they very likely will be important in understandingthe initiation of breast cancer, and especially its progression," Waldmansaid. "Another thing this allows us to do is one assay to examine theintegrity of the tumor DNA, and we expect that this measure will helppredict the clinical course of individual tumors."
In the study, the presence of multiple copies of DNA, called amplification,was detected in 20 of 33 breast tumors and in all 15 breast cancer celllines. But previously known regions of DNA amplification accounted for only22 percent of the observed amplifications in the tumors. Among previouslyunknown sites of amplification, the three most common contained amplifiedDNA, in from 15 percent to 20 percent of tumors examined.
By comparison, the ERBB2 breast cancer gene is overproduced in about20 percent of breast tumors.
CGH is not sensitive enough to identify specific genes with a role incancer, but gives a quick overview and a cell's genetic endowment andquickly narrows the search.
-- Jim Shrine
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