Technologies

Integrative Panel to Detect Mismatch Repair Deficiency

Proper detection of the genetic and epigenetic alterations underlying cancer is critical for correct diagnosis and selection of treatment plans. In particular, determination of whether an MMR-associated cancer arose due to inherited mutations or somatic lesions in essential for guiding treatment plans of patients and, in the case of inherited cancer syndromes such as Lynch Syndrome, monitoring of family members of patients. Here, we introduce a novel method of using hybrid-capture DNA sequencing to detect point mutations, insertions and deletions, copy number alterations, structural rearrangements, promoter methylation, and microsatellite instability (MSI) to enable diagnosis of various MMR-associated and related cancers. This hybrid-capture approach utilizes a novel targeted probe panel enabling simultaneous readout of all of the aforementioned clinically-relevant sources of genome variation. In contrast to existing methods, this technology eliminates the need for sequential testing by multiple independent and complex tests (e.g., IHC), which are often not available in a single laboratory. This technology, therefore, has the potential to bring significant time and cost savings while providing best-in-class data quality for the detection of diagnosis of MMR-associated cancers.

Schematic representation of Lynch Syndrome vs. sporadic (somatic) colorectal cancer with regards to inactivation of selective MMR genes. Source: Sinicrope, Nature Reviews Clinical Oncology (2010).