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'Personalized' genome sequencing reveals coding error in gene for inherited pancreatic cancer
Date:3/5/2009

available in this case," says Sin Jones, Ph.D., research associate at the Johns Hopkins Kimmel Cancer Center. Instead, the investigators used high-powered computer software to scan all known protein-coding genes in the patient -- approximately 20,000 of them to find more than 15,000 variations.

Most of the variations were normal ones coding for such things as eye or hair color, but the search was designed to track down particular mutations that caused certain proteins to be shortened, a process that commonly occurs in cancer, says James Eshleman, M.D., Ph.D., associate professor of pathology and oncology.

The search yielded one gene variant, PALB2, resulting from a substitution of a single DNA letter coding for cytosine with a different one that codes for thymidine.

The research team then scanned for the PALB2 gene in 96 other individuals with pancreatic cancer who each had at least one relative with pancreatic cancer. Three of them had coding errors in the PALB2 gene that shortened the protein in a similar way. She estimates that three percent of people with hereditary pancreatic cancer have mutations in PALB2, making it the second most common gene mutation in these patients after BRCA2.

The investigators believe that their approach could be used to identify inherited alterations that predispose people to other types of cancer as well as other genetic-based diseases. "The more information we have about normal variants, the easier it will be to find disease-causing ones," says Michael Goggins, M.D., professor of pathology, medicine and oncology at Johns Hopkins.

In the future, scanning genomes for hereditary disease-causing genes could become "reasonably routine," according to Bert Vogelstein, M.D., an investigator at the Howard Hughes Medical Institute and co-director of the Ludwig Center at Johns Hopkins.

The investigators say that the cost to determine the sequence of all genes in an individual for th
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Contact: Vanessa Wasta
wastava@jhmi.edu
410-955-1287
Johns Hopkins Medical Institutions
Source:Eurekalert

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