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Map Of Amplified Genome Region Clarified And New Gene Identified As Overexpressed In Oral Cancer, Report University Of Pittsburgh Researchers

PITTSBURGH, August 1, 2002 — Investigators from the University of Pittsburgh have used a new technique to map a region of the genome - chromosomal band 11q13 - that is present in extra copies, or amplified, in a large percentage of oral cancers. They also have identified a new gene that is expressed at abnormally high levels in oral cancers when the segment is amplified.

Their results are to be published the week of Aug. 5 online in the web version of Proceedings of the National Academy of Sciences (www.pnas.org/cgi/reprint/172285799b1).

"Gene amplification is a common and critically important genetic defect in cancer cells, and chromosomal band 11q13 appears to be one of the most frequently amplified chromosomal regions. Yet, until now, a comprehensive physical map of the band has not been published," said corresponding author Susanne M. Gollin, Ph.D., associate professor, department of human genetics, Graduate School of Public Health and director, Cytogenetics Facility, University of Pittsburgh Cancer Institute (UPCI).

"Our work represents the first time the structure of the 11q13 amplicon has been mapped so finely, enabling us to identify a new gene in this segment that is both amplified and overexpressed in oral cancer cells."

Amplification of band 11q13 appears to be a relatively common event in the development of oral and head and neck cancers, and it is usually associated with a poor prognosis. In addition to oral and head and neck cancers, amplification of the 11q13 region has been reported in breast, lung, bladder and esophageal cancers.

In this study, investigators examined 30 oral squamous cell carcinoma cell lines developed from tumors removed from patients who had not been treated previously. A new technique called quantitative microsatellite analysis (QuMA) was used to map the 11q13 amplicon, which houses about 10 genes. Of the cell lines examined, 16 (63 percent) had amplification of band 11q13. Also, a new gene - tumor amplified and overexpressed sequence 1 (TAOS1) - was discovered and noted to be overexpressed in cell lines with 11q13 gene amplification.

"The TAOS1 gene may prove to be a useful biomarker in the diagnosis and prognosis of oral cancers," said Dr. Gollin.

"Due to its versatility, accuracy and ability to produce high-resolution copy number measurements across the genome, QuMA should be helpful in examining this and other amplified genomic regions in a wide variety of tumors," said senior author Tony E. Godfrey, Ph.D., assistant professor of surgery and human genetics and director, UPCI TaqMan facility.

Dr. Gollin recently received a grant of $1.6 million from the National Institute for Dental and Craniofacial Research to conduct additional studies to further characterize the 11q13 amplicon and investigate the process of gene amplification in oral cancer cells.

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