Tuesday October 9, 2001

COMPANY PRESS RELEASE

Researchers Looking For Genetic Causes Of Breast Cancer Adopt High Throughput WAVE® System 3500HT From Transgenomic

WECARE Study Designed to Determine Connection Between ATM Gene, Radiation and Breast Cancer

SEATTLE, Wash., (Oct. 9, 2001) -Transgenomic, Inc., (Nasdaq: TBIO) announced today that the Virginia Mason-Research Center (VMRC) has upgraded to a WAVE® System 3500HT for genetic analysis to identify mutations that cause breast cancer. Researchers at VMRC are participating in an international multi-center study designed to identify mutations in the ATM gene that increase susceptibility to breast cancer.

Researchers at VMRC are participating in the WECARE Project, or Women's Environment, Cancer and Radiation Exposure, which is designed to examine the interaction of radiation exposure, the ATM gene and breast cancer. The objective of the study is to determine whether women who are ATM gene carriers and who have received radiation therapy to treat a tumor in one breast are at especially high risk of developing cancer in the other breast. Researchers at 15 labs worldwide plan to screen genomic DNA for ATM mutations in 700 women with bilateral (involvement of both breasts) breast cancer and 1,400 women with unilateral (single breast involvement) breast cancer in the U.S. and Denmark. One of four labs responsible for screening the DNA samples, the VMRC genetics lab has used WAVE Systems since 1998. All four labs in the study are currently using the WAVE System to ensure uniform methodology and speed the completion of the study.

"Since the frequency of ATM carriers is thought to be about one percent of the general population, there is potential that mutations in the ATM gene could be a significant factor increasing susceptibility to breast cancer. There is also evidence that cancer patients who are ATM heterozygotes (mutated in one allele of ATM) are slightly sensitive to radiation therapy. The purpose of this study is to determine the connection between the ATM gene and breast cancer," said Sharon Teraoka, Ph.D., staff scientist, Virginia Mason Research Center. "ATM is a very large gene with many different reported mutations. As a result, it is very difficult to characterize. The upgrade to the WAVE System 3500HT has been significant because it has enabled us to screen samples twice as fast with the same high accuracy and sensitivity we and the rest of the Consortium have come to expect from the WAVE System."

The WAVE System analyzes DNA samples for both known and unknown genetic mutations with greater sensitivity, accuracy, speed and cost-effectiveness than other techniques. Understanding variations in the genetic code is the vital link to the development of new medical diagnostic and therapeutic products. While individual traits, such as hair and eye color, are determined by normal genetic variations, abnormal variations or mutations can create disease states such as cancer or hereditary cystic fibrosis. By comparing mutations in the genome to the occurrence of diseases or particular traits, correlation can be made between genes and specific diseases or traits.

Establishing which genetic variations are normal and which can lead to diseases such as cancer requires screening samples from hundreds or thousands of individuals. Screening at this level requires a high accuracy, high throughput and economical technology. With upgrades including an integrated accelerator and dual plate auto sampler, the WAVE System 3500HT reduces cycle time from nearly eight minutes to less than four minutes per sample. This results in a significant increase in sample throughput.

The incidence of ataxia telangiectasia (A-T) has been estimated at 1 in 40,000-100,000 live births, while the gene frequency is believed to be as common as 1-3 percent of the general population. The disease A-T is autosomal recessive, meaning that each parent has one normal ATM gene copy and one mutated ATM gene copy and each gives the affected child the mutated ATM gene. Individuals with A-T have cerebellar degeneration, immune system defects, are highly radiation sensitive, and susceptible to cancer. While ATM heterozygotes are clinically normal, previous studies have shown that ATM carriers in A-T families are at increased risk for breast cancer.

According to Dr. Teraoka, while the connection between ATM, radiation and breast cancer is still a somewhat controversial area, it is extremely important to validate whether it translates to greater risk during exposure to ionizing radiation, such as diagnostic X-rays or radiation therapy. Researchers at Virginia Mason plan to use the WAVE System 3500HT to screen for ATM mutations and improve the ability to direct and customize radiation therapy without contributing to the disease.

"One of the major objectives of the genomics revolution has been to associate genetic mutations with various diseases such as cancer," said Collin D'Silva, CEO, Transgenomic. "We commend the WECARE consortium for their tireless work in this area and are proud that the WAVE System is serving a useful purpose in their significant research study."

The WAVE® System Technology

As efforts to sequence and annotate the human genome near completion, the WAVE System, unlike more conventional technologies, can detect genetic mutations without previous knowledge of their existence or position. As a result, the WAVE System provides researchers with a more accurate and efficient means of performing the experiments necessary to identify mutations and to correlate the relationships between mutations and diseases. Principal application areas include genetic mutation screening and detection and new paths in microbial, pharmaceutical, biotechnology, forensic, plant and animal research.

Since its introduction in late 1997, the WAVE System has been utilized extensively by leading research institutions worldwide. Today, WAVE Systems are used in leading genomics, academic, medical and biopharmaceutical research institutions worldwide, including: Harvard University, Stanford University, Baylor College of Medicine, University of Chicago, Fred Hutchison Cancer Facility, Mayo Clinic, National Cancer Institute, National Institutes of Health, Institut Curie, University of Cambridge, Wellcome Trust-Oxford University, Institut Gustave Roussy, SmithKline Beecham, Bristol-Meyers Squibb, Millennium Pharmaceuticals, Merck & Company, Novartis and Eli Lilly & Company.

The WAVE System, utilizing the method of DHPLC (denaturing high-performance liquid chromatography), analyzes previously identified genes for both known and unknown genetic variations, changes or mutations. Mutations identified by DHPLC may provide researchers with critical information about the cause, onset and progression of certain diseases.

Scanning for mutations in genes with the WAVE System relies on the specific binding of complementary strands to form a DNA double helix. If a mutation in a gene exists, a DNA heteroduplex (pairing of not fully complementary strands) is formed and the binding is less "tight." High temperatures can be used to denature (melt) the DNA double helix. If a mutation exists, the melting temperature of the heteroduplex will be lower than that of the homoduplex. Partially melted DNA can be easily separated from unmelted DNA homoduplexes (pairings of fully complementary strands) containing no mutation. This method of denaturing the DNA double helix is sensitive, fast, accurate and inexpensive when compared to DNA sequencing.

If the WAVE System screening detects a variation, researchers will often use traditional DNA sequencing to understand the mutation in more detail. Using the WAVE System in advance of DNA screening can help eliminate unnecessary, detailed analysis on DNA without mutations, saving time and money.

About Transgenomic

Transgenomic is headquartered in Omaha, Neb., and has offices in the United States, Europe and Japan. Major research and development facilities are located in San Jose, Calif., and Crewe, Cheshire, United Kingdom. The company provides innovative research tools to the genomics segment of the life sciences industry. These tools enable researchers to discover and understand variation in the human genetic code, or genome, in order to accelerate and improve drug development and diagnostics.

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