MSI detection in CRC

Introduction: Microsatellite instability (MSI) occurs across a number of cancers and is associated with Lynch syndrome and different clinical characteristics, outcomes and response to therapies when compared to microsatellite stable (MSS) cancers. Routine MSI testing is now recommended for a number of cancer types including colorectal cancer (CRC). Using gene panels for sequencing of known cancer mutations is routinely performed to guide treatment decisions. By adding a number of MSI regions to a small gene panel, the efficacy of simultaneous MSI detection in a series of CRCs was tested. Methods: FFPE tumours were retrieved from Histopathology departments across Yorkshire and the Humber, from consented patients recruited into the Yorkshire Cancer Research Bowel Cancer Improvement Programme (YCRBCIP). Bowel cancers (n=335) were sequenced using a 23-gene panel kit (ATOM-Seq) provided by GeneFirst. The mismatch repair (MMR) status was obtained for each patient, from their routine pathology reports. Results: By testing 29 microsatellite regions in 335 samples the MSI/MSS status in 314/319 samples were correctly classified (98.4% concordance), with 16 not producing enough sequence to test. By reducing in silico the number of regions, comparable performance could be reached with as few as eight MSI marker positions. Discussion: This test represents a quick, and accurate means of determining MSI status in FFPE CRC samples, as part of a routine gene mutation assay, and can easily be incorporated into a research or diagnostic setting.