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Gene Study Reveals New Cancer-Related Mutations

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  • Gene Study Reveals New Cancer-Related Mutations

    http://www.cancer.org/docroot/NWS/co..._Mutations.asp

    <TABLE cellSpacing=0 cellPadding=0 width=440 border=0><TBODY><TR><TD class=T8 colSpan=2>Could Provide Targets for Drug Development</TD></TR><TR><TD colSpan=2 height=10></TD></TR></TBODY></TABLE><!-- END SECTION A; HEA MODULE --><TABLE cellSpacing=0 cellPadding=0 width="100%" border=0><TBODY><TR><TD class=T3 vAlign=top><!-- BEGIN News Article Date -->Article date: 2006/09/08

    </TD></TR><TR><TD vAlign=top width=440><!-- BEGIN SECTION B --><TABLE cellSpacing=0 cellPadding=0 width=150 align=right border=0><TBODY><TR><TD rowSpan=4></TD><TD></TD></TR><TR><TD></TD></TR></TBODY></TABLE>Summary: Researchers from Johns Hopkins University and other institutions have identified scores of gene mutations that play a role in breast cancer and colorectal cancer. This knowledge could one day help doctors better understand how these diseases form, and could lead to the development of drugs to treat them. The findings appear in Science Express, the early online edition of the journal Science.

    Why it's important: Breast and colorectal cancers account for more than 2 million cancer cases and around 940,000 deaths worldwide. In the US, breast cancer is expected to strike more than 200,000 women and kill nearly 41,000 this year alone.

    Colorectal cancer is expected to strike nearly 150,000 Americans and kill more than 55,000 this year. Researchers are searching for more clues as to how these cancers develop in hopes of finding new ways to prevent and treat them.

    "We are convinced that this kind of study will provide one of the best road maps possible for beating cancer," said study coauthor Kenneth Kinzler, PhD, professor of oncology and co-director of the Ludwig Center at Johns Hopkins. "Who would pass up the opportunity to read the enemy's game plan?"

    What's already known: Researchers have already identified some genes that are involved in the development of each of these cancers. For instance, mutations in the BRCA1 and/or BRCA2 genes make women (and men) more likely to develop breast cancer. Changes in a gene called APC are responsible for familial adenomatous polyposis, a condition that causes people to develop hundreds of colon polyps and puts them at high risk of developing colon cancer.

    Until now, however, no one had sequenced the entire genome of these cancers in hopes of finding all -- or at least many -- of the gene changes that might cause these diseases.

    How this study was done: The research team began with samples from 11 breast tumors and 11 colon tumors. Using sophisticated gene sequencing techniques, they compared more than 13,000 genes in the cancer samples to genes from normal breast and colon samples, looking for mutations. To narrow the field even more, they compared those mutations to samples from other cancers of the same type. Finally, they used a statistical calculation to figure out which of the hundreds of mutations they'd found were likely to contribute to cancer.

    What was found: In the end, the team identified 122 genes likely involved with breast cancer and 69 genes likely involved with colon cancer -- much more than the handful they had expected. Some of the genes they found were already known or suspected to be associated with cancer, but most had not been linked to the disease previously.

    The researchers also determined that the mutations found in breast cancer are very different from those found in colon cancer. That could be one reason that different cancers behave so differently in people, and why even tumors of the same type vary dramatically from person to person, they said. Their results also suggest that it takes many more mutations than previously believed to stimulate a cancer.

    The researchers caution that their work is just a first draft of the breast and colon cancer genomes. The techniques they used were not able to analyze every single gene there is -- around 5,000 were not included in the study -- and they could not identify every possible type of mutation. There could be more genes with different mutations that also play a role in these cancers.

    The bottom line: Although a lot of work remains to be done, this genome research has many implications for cancer diagnosis and treatment in the future, said Len Lichtenfeld, MD, deputy chief medical officer of the American Cancer Society.

    "This report brings us one more step down the line in understanding cancer processes and toward the development of new methods for truly early diagnosis," he said. "This [work] will also lead the way to new approaches in determining the prognosis of individual cancers, and enable us to create personalized therapeutic 'targeted cocktails' for the treatment of patients with cancer."

    The researchers agree that identifying targets for new drugs will be an important application of these findings. But that's not all. Knowing about the genes involved with these 2 cancers can help scientists figure out exactly what factors cause the mutations that lead to different cancers (perhaps things in the environment, or in our diets) and maybe lead to better ways of preventing these diseases.

    "Just as sequencing the human genome laid the groundwork for subsequent research in genetics, these data lay the foundation for decades of research on colon and breast cancers, " said study coauthor Victor Velculescu, MD, PhD, assistant professor of oncology at the Johns Hopkins Kimmel Cancer Center.
    Their technique can also be used to identify mutated genes in other cancer types, Velculescu and colleagues said, potentially opening the door to more treatments for more people.
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    "The next major advancement in the health of American people will be determined by what the individual is willing to do for himself"-- John Knowles, Former President of the Rockefeller Foundation
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