125PTumour mutation burden and microsatellite instability in colorectal cancer

Abstract Background The role of tumour mutation burden (TMB) as predictive biomarker of response to immune checkpoint inhibitors (ICI) is being explored in colorectal cancer (CRC). Microsatellite instability status (MSI) is currently used to identify CRC patients who may benefit from ICI. However, TMB values vary significantly among MSI CRC. In addition, selected microsatellite stable (MSS) with high TMB might also benefit treatment with ICI. Methods TMB evaluation was performed with the Oncomine Tumor Mutation Load Assay (OTML, Thermofisher) on the Ion S5XL platform. Data analysis was carried out using Ion Reporter Software v5.10. TMB was calculated as the total number of non-synonymous somatic single nucleotide variants (SNVs) and indels divided by number of bases sequenced. MSI status was analysed by means of the Idylla MSI assay (Biocartis), which evaluates the presence of mutations in 7 novel MSI loci. Results TMB analysis was performed on 106 formalin-fixed paraffin embedded CRC samples and the data were compared with the MSI results. The Idylla assay classified 68 samples as MSS and 38 samples as microsatellite instable (MSI-H). The TMB values ranged from zero to 21.22 (median: 5.005) in the MSS and from 13.42 to 204.8 in the MSI-H group (median: 25.66), with a significant difference in median values (P  Conclusions The TMB values assessed with the OTML assay strongly correlated with MSI status in CRC. However, significant heterogeneity in TMB levels were detected among both MSI and MSS tumors, suggesting that TMB testing might provide additional information on sensitivity to ICI in CRC. The correlations with driver gene alterations might help in selecting tumors to be tested for TMB. Legal entity responsible for the study The authors. Funding Has not received any funding. Disclosure All authors have declared no conflicts of interest.