Integrative Analysis of Hereditary Nonpolyposis Colorectal Cancer: the Contribution of Allele-Specific Expression and Other Assays to Diagnostic Algorithms
Figure 2
Results of integrative germline analyses performed in this study.
VUS included in-frame deletions, sequence variants with uncertain effect on splicing and missense variants. Evidence of a pathogenic, possibly pathogenic defect in 28 probands with VUS derived from previous studies (see Table S5). In one additional case (360#2916) availability of RNA allowed ASE analysis that helped to characterize a VUS shared also by another proband (986#3487, see Results). ASE analysis was conducted in 22 individuals, including 12 with ascertained germline defect that are not shown in the figure. APC and MUTYH screening was conducted in a subset of patients negative for MMR defects (see Methods). Inclusion of ASE analysis and screening for APC and MUTYH sequence variants in the integrative analyses increased the number of probands with germline alterations detected.