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Powerful new method helps reveal genetic basis of cancer

In 1981, using a gene transfer method he pioneered, Wigler, working at Cold Spring Harbor Laboratory, discovered one of the first human oncogenes (the H-ras oncogene). Hyperactive or excess Ras protein, or alterations in cell functions related to Ras, are implicated in the majority of cancers. Today, cancer therapies that target components of the Ras pathway (e.g. farnesyltransferase inhibitors) are in clinical trials.

In 1993, Wigler and Nikolai Lisitsyn developed a powerful and versatile gene discovery method called Representational Difference Analysis (RDA). RDA enables researchers to "clone the differences" between any two sets of DNA (for example, normal versus tumor DNA isolated from the same patient, or uninfected cells versus cells infected with an unknown virus).

Since 1993, Wigler's lab, alone and in collaboration with groups at Columbia University and Tularik, Inc., has used RDA to identify several previously unrecognized oncogenes and tumor suppressors genes, primarily from sporadic breast cancers (the most common form of the disease). These include PTEN and DBC2 (tumor suppressor genes frequently missing from or inactive in a large proportion of breast and other cancers) in addition to KCNK9 (a gene whose identification revealed a previously unrecognized mechanism for oncogene action as well as an attractive therapeutic target, namely, potassium channels).

The new method, ROMA, is essentially "RDA on a chip." Combining RDA and DNA microarray analysis with the third "pillar" of the method--i.e. knowledge of the complete human genome sequence--gives ROMA unprecedented ability to detect copy number fluctuations on a genome-wide scale.


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Contact: Peter Sherwood
sherwood@cshl.edu
516-367-6947
Cold Spring Harbor Laboratory
15-Sep-2003


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