@article {Redford305383, author = {Lisa Redford and Ghanim Alhilal and Stephanie Needham and Ottie O{\textquoteright}Brien and Julie Coaker and John Tyson and Leonardo Maldaner Amorim and Iona Middleton and Harsh Sheth and Osagi Izuogu and Mark Arends and Anca Oniscu and {\'A}ngel Miguel Alonso and Sira Moreno Laguna and Mauro Santibanez-Koref and Michael S. Jackson and John Burn}, title = {A novel panel of short mononucleotide repeats linked to informative polymorphisms enabling effective high volume low cost discrimination between mismatch repair deficient and proficient tumours}, elocation-id = {305383}, year = {2018}, doi = {10.1101/305383}, publisher = {Cold Spring Harbor Laboratory}, abstract = {Somatic mutations in mononucleotide repeats are commonly used to assess the mismatch repair status of tumours. Current tests focus on repeats with a length above 15bp, which tend to be somatically more unstable than shorter ones. These longer repeats also have a substantially higher PCR error rate and tests that use capillary electrophoresis for fragment size analysis often require expert interpretation. In this communication, we present a panel of 17 short repeats (length 7{\textendash}12bp) for sequence-based microsatellite instability (MSI) testing. Using a simple scoring procedure that incorporates the allelic distribution of the mutant repeats, and analysis of two cohort of tumours totalling 209 samples, we show that this panel is able to discriminate between MMR proficient and deficient tumours, even when constitutional DNA is not available. In the training cohort, the method achieved 100\% concordance with fragment analysis, while in the testing cohort, 4 discordant samples were observed (corresponding to 97\% concordance). Of these, 2 showed discrepancies between fragment analysis and immunohistochemistry and one was reclassified after re-testing using fragment analysis. These results indicate that our approach offers the option of a reliable, scalable routine test for MSI.}, URL = {https://www.biorxiv.org/content/early/2018/04/20/305383}, eprint = {https://www.biorxiv.org/content/early/2018/04/20/305383.full.pdf}, journal = {bioRxiv} }