Swedish Study Shows Superior Performance of QIAGEN Inc. Pyrosequencing in KRAS Mutation Detection

VENLO, THE NETHERLANDS--(Marketwire - May 29, 2009) - A clinical study recently conducted by the Uppsala University Hospital, Sweden, has shown that QIAGEN’s PyroMark KRAS CE assay detects the expected number of mutations in codons 12 and 13 and an unexpected high number in codon 61 of the KRAS gene. In one case, even an additional new and relevant mutation was detected in codon 60. KRAS is an oncogene which plays a crucial role in the development of tumors. Pyrosequencing is also the method of choice for mutation analysis of other important oncoproteins such as B-Raf, EGF-Receptor as well as epigenetic biomarkers.

Studies have shown that KRAS mutation testing can help define which CRC patients will benefit from treatment with epidermal growth factor receptor (EGFR) inhibiting monoclonal antibodies, such as Amgen’s Vectibix (panitumumab) and Imclone/Bristol-Myers Squibb/Merck KgaA’s Erbitux (cetuximab). Established clinical guidelines describe treatment of metastasized colon cancer for patients with the unmutated KRAS gene only.

The results of the study confirm that the quantitative Pyrosequencing assay detects more mutations including those most common in codons 12, 13, and 61 (which are not fully covered by PCR) than PCR-based tests for KRAS mutation. Furthermore, it was verified that the use of the Pyrosequencing technology allows detection not only of known, but also the discovery of unknown mutations and can therefore adapt to emerging insights into optimized use of EGFR inhibitor therapeutics.

The PyroMark assay includes reagents and controls and runs on the PyroMark instrument which uses comprehensive analysis software. Easy, robust handling combined with turn-around of less than 6 hours from sample to result for up to 96 samples enables adoption of Pyrosequencing in every clinical research and diagnostic laboratory.

The Swedish researchers have also shown that the success rate of Pyrosequencing in detecting mutations is higher and less dependent on DNA quality than other technologies, including real-time PCR and Sanger sequencing. This suggests that the rate of mutated KRAS gene might in fact be higher than previously found. The study details are expected to be published shortly.

“The ability of Pyrosequencing to detect and quantify both known and unknown genetic as well as epigenetic mutations occurring in short stretches of genes makes this technology the premier choice for assays enabling personalized cancer treatment,” said Thomas Schweins, VP Marketing and Strategy, QIAGEN. “This technology allows researchers to examine populations of patients and helps them group them into sub-populations with similar characteristics in order to provide them efficacious treatment. We are very pleased that this was also evidenced by a record number of publications on, and a significant level of excitement for, Pyrosequencing at ASCO.”

“PyroMark is part of our overall commitment to helping researchers continue to make discoveries in regards to cancer treatment and to clinicians who are in search of a platform that can address with previously not possible performance parameters genetic, pathogen and epigenetic analyses in molecular testing,” Dr. Schweins continues. “QIAGEN is pursuing novel test panels that enable stage specific prognosis, advance the clinical practice of personalized medicine, and will ultimately help deliver safe, effective treatment to cancer patients.”

In addition to mutations in the KRAS genes, research has uncovered mutations in the B-RAF and the EGFR genes seem to contribute to the effectiveness of anti-EGFR drug treatments. To meet this need, QIAGEN expands its Pyrosequencing portfolio with assays for B-RAF and EGFR. PyroMark BRAF reveals both the V600E mutation (responsible for 90% of mutations in human cancers) as well as other mutations surrounding this position in exon 15 of the B-RAF gene. In addition, rare mutations in exon 11 can be analyzed. The EGFR assay covers a long fragment of the EGFR gene and provides the mutation status of codons 858 and 719 as well as the status on certain insertions and deletions in that region which are associated with effectiveness of anti-EGFR drugs.

About KRAS

KRAS is an oncogene which plays a crucial role in the development of tumors. Mutations in the RAS family of proto-oncogenes (comprised of HRAS, NRAS and KRAS) are very common, being found in up to 30 % of all human tumors. Mutations in the KRAS gene result in a KRAS protein that is permanently active. Such oncogenic activation has been suggested to be involved in many aspects of the development and progression of cancer, including abnormal cell growth, proliferation, and differentiation, as well as increased invasion and metastasis. Mutant KRAS is present in approximately 35-45 % of metastatic colorectal cancers (CRC). The demand exists for a robust, fast, sensitive method to detect activating mutations of the KRAS gene in clinical samples

About QIAGEN:

QIAGEN N.V., a Netherlands holding company, is the leading global provider of sample and assay technologies. Sample technologies are used to isolate and process DNA, RNA and proteins from biological samples such as blood or tissue. Assay technologies are used to make such isolated biomolecules visible. QIAGEN has developed and markets more than 500 consumable products as well as automated solutions for such consumables. The company provides its products to molecular diagnostics laboratories, academic researchers, pharmaceutical and biotechnology companies, and applied testing customers for purposes such as forensics, animal or food testing and pharmaceutical process control. QIAGEN’s assay technologies include one of the broadest panels of molecular diagnostic tests available worldwide. This panel includes the digene HPV Test, which is regarded as the “gold standard” in testing for high-risk types of human papillomavirus (HPV), the primary cause of cervical cancer. QIAGEN employs more than 3,000 people in over 30 locations worldwide. Further information about QIAGEN can be found at http://www.qiagen.com/.