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Gene’s Mountains and Hills | Cancer October 21, 2007

Posted by ramunas in breast cancer, cancer genetics, colon cancer, research.
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A picture of huge (and ugly) macro-anatomical sample of cancer is an often finding in some chapters of textbook about cancer genetics. It has no educational value from a present personalized medicine perspective. A picture of expression profiling or mutated genes provides more relevant and contemporary understanding.

Here is how an individual colon cancer from a patient Mx38 looks like (source):

Kind of avantgarde picture in an early 20 century? Don’t worry – it will go mainstream soon like a pop-art cartoon…

A researchers team lead by notorious Bert Vogelstein (co-author of colorectal cancer mutagenesis model) performed (second) amazing study – they sequenced several individual cancers DNA:

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 cancer’s key characteristics, and most of these genes may be different for each patient (via).

These data suggest a genetic landscape dominated by genes that each are mutated in relatively few cancers:

“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.

It looks like “few mountains surrounded by many hills.”

Surprisingly, 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 cancer’s key characteristics, and most of these genes may be different for each patient.

Lot of texbooks state, that c.a. 7-8 genes are mutated in colon cancer. And they were ten-fold  wrong: mutations in 77 for colon and 81 genes for breast cancer are required to develop.

The scientists say that directing therapies at common pathways that are linked by both prevalent and rare gene mutations is a better approach than aiming treatments at specific genes. They also note that personalized cancer genomics paves the way for tailored therapies and diagnostics focusing on the alterations identified in a particular patient’s cancer. Many of the mutations identified by scientists could be important in developing individualized cancer vaccines and monitoring patients for early recurrence of their disease.

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