Additional file 1 of A tumor focused approach to resolving the etiology of DNA mismatch repair deficient tumors classified as suspected Lynch syndrome
Creators: name: Walker, Romy
name: Mahmood, Khalid
name: Joo, Jihoon E.
name: Clendenning, Mark
name: Georgeson, Peter
name: Como, Julia
name: Joseland, Sharelle
name: Preston, Susan G.
name: Antill, Yoland
name: Austin, Rachel
name: Boussioutas, Alex
name: Bowman, Michelle
name: Burke, Jo
name: Campbell, Ainsley
name: Daneshvar, Simin
name: Edwards, Emma
name: Gleeson, Margaret
name: Goodwin, Annabel
name: Harris, Marion T.
name: Henderson, Alex
name: Higgins, Megan
name: Hopper, John L.
name: Hutchinson, Ryan A.
name: Ip, Emilia
name: Isbister, Joanne
name: Kasem, Kais
name: Marfan, Helen
name: Milnes, Di
name: Ng, Annabelle
name: Nichols, Cassandra
name: O’Connell, Shona
name: Pachter, Nicholas
name: Pope, Bernard J.
name: Poplawski, Nicola
name: Ragunathan, Abiramy
name: Smyth, Courtney
name: Spigelman, Allan
name: Storey, Kirsty
name: Susman, Rachel
name: Taylor, Jessica A.
name: Warwick, Linda
name: Wilding, Mathilda
name: Williams, Rachel
name: Win, Aung K.
name: Walsh, Michael D.
name: Macrae, Finlay A.
name: Jenkins, Mark A.
name: Rosty, Christophe
name: Winship, Ingrid M.
name: Buchanan, Daniel D.
Publisher: name: figshare
Year: 2023
Subjects: subject: Biophysics
subject: Medicine
subject: Cell Biology
subject: Genetics
subject: FOS: Biological sciences
subject: Molecular Biology
subject: Biotechnology
subject: Cancer

description: Additional file 1: Table S1. Table displaying optimal cut-offs for the six tumor features determined previously (Walker et al. 2023) in the additive feature combination approach. Table S2. SLS tumors (n=13) that showed discordant MMR IHC findings between clinical diagnostic testing before study entry and testing completed internally during this study and the change in their MMR status and/or pattern of MMR protein loss. Table S3. The concordance between the final MMR IHC result and the predicted dMMR status from the additive feature combination approach overall and by tumor type. Table S4. The tumor MLH1 methylation testing completed for SLS tumors prior to entering the study showing either negative, inconclusive, or not tested results and the subsequent MLH1 methylation testing results from internal testing using MethyLight and MS-HRM assays highlighting the positive MLH1 methylation results found by this study. Table S5. Presentation of germline pathogenic variants and variants of uncertain clinical significance (VUS) identified in the MMR, MUTYH and POLE genes. Table S6. Summary of the clinicopathological features for the double somatic MMR mutation (dMMR-DS) tumors overall and by tumor type. Figure S1. Bar plots presenting the results from the additive tumor feature combination approach to assess the MMR status in the double somatic mutation cohort for A) all tumors combined and separated by B) CRC, C) EC and D) SST tissue types. Figure S2. Bar plot presenting the prevalence of pathogenic/likely pathogenic somatic mutations (including loss of heterozygosity, LOH) by subtype for the study cohort. Figure S3. Pie graphs displaying the frequency of the mutation combination type (two single somatic mutations versus a single somatic mutation with loss of heterozygosity (LOH)) as well as the type of mutation A) overall and B) separated by tissue type. Figure S4. Bar graphs presenting the site distribution in the double somatic mutation cohort across all CRCs and SSTs. Figure S5. Boxplots presenting the site distribution in the double somatic mutation cohort across all A) CRCs and B) SSTs. Significant (&lt; 0.05) p-values are indicated for pairwise (t-test) and multigroup comparisons (Anova). Figure S6. Scatter plots presenting the PREMM5 score distribution in the test cohort for A) all tumors combined and separated by B) CRC, C) EC and D) SST tissue types. Figure S7. The distribution of tumor values for each of the six features that are included in the additive feature combination approach for determining tumor dMMR status grouped by molecular subtype and by combining sporadic dMMR groups dMMR-DS and dMMR-MLH1me into a “sporadic combined” group.