Gene deletion drives more than a quarter of breast cancers


View:292 Time:2012-08-16


Recent studies have observed loss of the gene NF1 in glioblastoma (an aggressive brain cancer), lung and ovarian cancers, but the significance has been overlooked because it was thought that two copies of the gene (one from each parent) needed to be missing to cause cancer. The study, published online July 30 in the journal Genetics, reports that in most human breast cancer cases where NF1 is a factor, only one copy is missing.

The finding has important clinical implications. It suggests that several existing drugs may be effective in treating breast cancers with missing NF1; it also suggests that the commonly used breast cancer drug tamoxifen could make the disease worse in these specific cancers.

The NF1 gene negatively regulates one of the most important oncogenes -- genes that when mutated or expressed at high levels contribute to turning a normal cell into a cancerous one. This oncogene, called RAS, is involved in signaling inside the cell to control growth. When NF1 is missing or depleted, RAS becomes hyperactivated and can lead to tumor formation.

In the study, Cornell researchers used a mouse model with elevated mutation rates that lead to breast cancer in 80 percent of the mice.

"These mice almost always get mammary tumors, and when we looked at their genomes, nearly all of them were missing this NF1 gene," said John Schimenti, professor of genetics and the papers senior author. "There are many big cancer studies that identify the most commonly mutated genes, but they dont prove experimentally that those genes are the drivers of cancer."
 
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