Genome update defines landscape of breast and col...( One year after completing the first ...)

One year after completing the first large-scale report sequencing breast and colon cancer genes, Johns Hopkins Kimmel Cancer Center scientists have studied the vast majority of protein-coding genes which now suggest a landscape dominated by genes that each are mutated in relatively few cancers.

Their report, published online in the October 11 issue of Science Express, indicates that while little is known about these less-commonly mutated genes, they can be grouped into clusters according to their pathways.

There are gene mountains represented by those that are frequently altered and have been the focus of cancer research for years, in part because they were the only genes known to contribute to cancer, says Bert Vogelstein, M.D., an investigator at the Howard Hughes Medical Institute and co-director of the Ludwig Center at Johns Hopkins. Now, we can see the whole picture, and it is clear that lower peaks or gene hills are the predominant feature.

In a systematic search of 18,191 genes representing more than 90 percent of the protein-coding genes in the human genome -- about 5,000 more than in the first screen -- the Johns Hopkins scientists found that most cancer-causing gene mutations are quite diverse and can vary from person to person. They found that an average 77 genes are mutated in an individual colon cancer and 81 in breast cancer. Of these, about 15 are likely to contribute to a cancers key characteristics, and most of these genes may be different for each patient.

Fifteen years ago, we said the p53 gene was the most commonly mutated gene in cancer. Its amazing that this is still true, says Kenneth W. Kinzler, Ph.D., professor of oncology at Hopkins Kimmel Cancer Center.

With no more higher-frequency mutations on the horizon, the investigators say that personalized medicines may now focus on the more complicated pathways that link these less-commonly mutated genes.

As an example, the Hopkins
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