BioWorld International Correspondent

PARIS - French researchers have discovered a new genetic explanation for the development of colon cancer, which contradicts the conventional assumption that mutation of the APC gene is the starting point for that cancer.

Researchers at France's National Scientific Research Center (CNRS) and the National Institute of Health and Medical Research (Inserm), led by Daniel Louvard of the Institut Curie, a leading Paris-based cancer research and treatment center, demonstrated in a mouse model that the mutation of the k-ras gene in cells of the large intestine resulted in 80 percent of the mice developing colon cancer without any mutation of the APC (adenomatous polyposis coli) gene.

The APC gene, which is mutated in 80 percent of humans suffering from colon cancer, is one of four genes that are associated with the development of the disease. The others are the k-ras oncogene, which is mutated in 50 percent of cases; the DCC (deleted in colon carcinoma) gene, which codes for a transmembrane protein and is altered in 70 percent of cases; and the p53 tumor suppressor gene, which is mutated in 70 percent of colon cancer patients.

While the chronological order of the occurrence of those mutations has been open to doubt, alteration of the APC gene generally has been regarded as the initiator of tumor development up to now since, once mutated, it triggers an excessive proliferation of cells. The latest findings of Louvard's team turn conventional wisdom on its head. As well as demonstrating that colon cancer can develop without any mutation of the APC gene, their research also found that in 40 percent of the mice that developed tumors, the p53 gene also was mutated, suggesting that the k-ras and p53 genes may cooperate in the development of colon cancer.

Louvard now plans to use his transgenic mice to monitor tumor growth in vivo using magnetic resonance imaging technology, as well as to test the efficacy of new therapies, regarding the animals as an excellent preclinical model for identifying novel therapeutic targets.