Friday October 15, 1999

COMPANY PRESS RELEASE

German Breast Cancer Centres Choose the WAVE® Nucleic Acid Fragment Analysis System from Transgenomic, Inc.

Germany's twelve Breast Cancer (BRCA1) Centres have chosen the WAVE® Nucleic Acid Fragment Analysis System from Transgenomic for a national large scale mutation screening programme in hereditary breast and ovarian cancers. The WAVE® Nucleic Acid Fragment Analysis System has proved to be much faster and more accurate than traditional methods.

Priv.-Doz. Dr. Norbert Arnold, Dr. Eva Gross and Priv.-Doz. Dr. Marion Kiechle evaluated the WAVE® Nucleic Acid Fragment Analysis System for the BRCA1 Centres over a one year period at Kiel University. The evaluation was sponsored by the German Cancer Aid (Deutsche Krebshilfe), and looked at several technologies including SSCP (single-strand conformation polymorphism) and direct sequencing. The aim was to find suitable technology that offered sensitivity, reliability and economy, which could be automated for high throughput screening.

Priv.-Doz. Dr. Norbert Arnold said: "The operating costs of the WAVE system, which uses the method of denaturing high performance liquid chromatography (DHPLC), are 10 times lower than those of direct sequencing. Additionally, DHPLC analysis is eight times faster than direct sequencing. Typically BRCA1 mutation results can be obtained in one day using the WAVE® Nucleic Acid Fragment Analysis System, with 96 samples running unattended overnight. DHPLC offers a reliable and sensitive means for the detection of BRCA1 mutations, as researchers only need to distinguish between single and multiple peaks in the elution profile."

The DNA samples used in the evaluation were taken from 80 patients with suspected familial cancer, who had asked for genetic counseling. 10,000 DNA fragments, varying in size from 200 to 600bp, were amplified from exons of the BRCA1 gene and analyzed on the WAVE® Nucleic Acid Fragment Analysis System. Evaluation included establishing the optimum conditions for new mutations.

All DHPLC analyses were performed blind to mutation status, and on all runs, a positive control fragment with a known sequence variation was used as a positive control to check resolution of heteroduplex peaks. Temperature was the main determinant of the quality of results from any primer pair, so analyses requiring the same temperature were run at the same time.

All sequence alterations were easily detected using DHPLC with the WAVE® Nucleic Acid Fragment Analysis System, compared to 94 per cent for SSCP. All mutations in the BRCA1 gene also gave a distinctive profile on the WAVE® Nucleic Acid Fragment Analysis System, with no false positive or negative results recorded. Results were therefore easy to interpret. The peaks on the chromatogram of the eluted DNA fragment showed a characteristic pattern for each different sequence alteration. Sequencing was then performed to confirm DHPLC results and, for known genetic variations, no discrepancies were found between the DHPLC prediction and the actual sequencing result.

The WAVE® Nucleic Acid Fragment Analysis System has proved invaluable to the Breast Cancer Centres as mutation analysis of the BRCA1 gene is a complex matter. Many additional WAVE® Nucleic Acid Fragment Analysis System units have already been ordered and installed and screening has begun in earnest.

More information about the evaluation can be obtained from the following publications:
"A comparison of BRCA1 mutation analysis by direct sequencing, SSCP and DHPLC." Gross, E., Arnold, N., Goette, J., Schwarz-Boeger, U. and Kiechle, M. Human Genetics (1999) 105, 72-78.

"A highly sensitive, fast and economical technique for mutation analysis in hereditary breast and ovarian cancers." Arnold, N., Gross, E., Schwarz-Boeger, U., Pfisterer, J., Jonat, W., and Kiechle, M. Human Mutation (1999) in press.

Transgenomic Inc., of San Jose, California, is a leading edge designer and manufacturer of state-of-the-art scientific instruments. Transgenomic's advances in biotechnology offer DNA and RNA fragment separation for mutation screening, functional genomics and genotyping for applications in basic research, diagnostics and forensics in laboratories worldwide.

Certain statements made by Transgenomic, Inc. in this press release may be forward looking. These may be identified by the use of forward-looking words or phrases such as in the following examples: "anticipate," "believe," "estimated," "think," "planned," "potential," "should," others. Any forward-looking statements are based on the Company's current expectations. The Company undertakes no obligation to publicly release the results of any revisions to any forward looking statement, which may be made to reflect events or circumstances after the date hereof or to reflect the occurrence of unanticipated events. Statements in this release should be evaluated in light of these important factors.

WAVE is a registered trademark of Transgenomic, Inc.

For more information contact info@transgenomic.com.