Agena Bioscience expands ultrasensitive somatic mutation detection technology

Agena Bioscience, Inc., which recently acquired the Bioscience business of Sequenom, Inc., today announced expansion of the UltraSEEK™ technology, the first ultrasensitive somatic mutation detection technology for high-throughput and definitive interrogation of rare mutations that occur at less than 1% abundance in matched tissue, circulating plasma, and tumor samples. The first panel made available this year, the UltraSEEK Oncogene Panel, uses 40 nanograms of input DNA to interrogate 26 driver mutations in 12 critical oncogenes. An online tool for designing custom UltraSEEK panels for ultrasensitive interrogation of low-level mutations on the MassARRAY® System will be available to the clinical research community later this year.

Tumors harbor many cells with differing genetic mutations. While some of these cells may contain mutations that confer resistance to targeted inhibitors, they may compose such a miniscule component of the tumor that these cells are not detected using standard genotyping and sequencing methodologies. Those methodologies have analytical sensitivity limited to mutations at 5–10% abundance. Additionally, they restrict analysis to solid tumor samples and force compromise between sample number and depth of coverage. In the rare case low-level mutations were detected using newer methodologies such as digital PCR, few if any studies have addressed the utility of these low-level mutations in the context of therapeutic response. 

The UltraSEEK technology enhances the sensitivity of the single-allele base extension reaction (SABER) method for MassARRAY genotyping. The SABER method was recently employed by Dr. Kazuto Nishio and colleagues at Kinki University in Osaka, Japan and several Japanese medical centers to profile lung cancer-related gene fusions and rare somatic hotspot mutations that may affect patients' therapeutic responses in a phase III trial of multiple lung cancer drugs. Data from the study will be presented at the American Society for Clinical Oncology (ASCO) annual meeting in Chicago on Saturday, May 31.

"UltraSEEK puts us on the cusp of understanding how to treat chronic diseases. For investigators interested in liquid biopsies to monitor therapeutic response, the unsurpassed sensitivity and throughput that the UltraSEEK technology affords allows acquisition of the biological data necessary to address resistance to targeted inhibitors and/or minimal residual disease," said John Lillig, the Chairman and interim CEO of Agena Bioscience.

"Certain cancer therapeutics are extremely effective at shrinking specific tumor types, such as treating non-small-cell lung cancer with anti-EGFR inhibitors. Dr. Nishio's study indicates that detecting in blood plasma a low-level mutation such as T790M, which occurs at a frequency sometimes below 0.5%, may indicate future tumor regrowth and the need to assess an alternative treatment plan," said Lillig.

The UltraSEEK method employs a PCR reaction followed by an extension reaction. The extension reaction utilizes a single mutation-specific chain terminator labeled with a moiety for solid phase capture. After capture, wash, and elution, products are spotted onto a research-use-only SpectroCHIP® Array for MALDI-TOF analysis on any MassARRAY System. The method can be conducted on 96-well and 384-well plates, the smaller of which accommodates up to 24 samples to facilitate studies comparing multiple sample types.

The entire workflow for the UltraSEEK panels, from extracted sample DNA to the final mutation report, can be completed in a single day.

The UltraSEEK Oncogene Panel and MassARRAY System are For Research Use Only. Not for use in diagnostic procedures.