DCP hypothesizes that recurrent frame-shift mutations, as observed in Lynch Syndrome, will also occur in Constitutional Mismatch Repair Deficiency (CMMRD) and that the neoantigen vaccine strategy and reagents already under development by DCP will be relevant to cancer prevention in CMMRD Syndrome. To test this hypothesis, DCP is conducting targeted next generation sequencing using a panel of ~30 mononucleotide repeat loci in samples of normal mucosa, tumor tissue, blood (cfDNA and RNA), and fecal DNA from the Pms2 mutant mouse model (GEMM). This will establish the relevance of the mouse model to the available Lynch Syndrome vaccines. If the current vaccines are relevant, they will be tested for cancer preventive efficacy in the GEMM. A biospecimen collection of human samples is needed for the next stage. Specimens from the collection will be sequenced using an expanded panel of ~120 mononucleotide repeat loci. Based on the results, consideration will be given to creation of a new frame-shift vaccine or expanding planned Lynch Syndrome cancer prevention trials to include CMMRD and particularly the high-risk Inuit cohort. The downstream work for generation of sequencing libraries, analysis, and data reporting for human samples obtained for this biospecimen collection will be performed under the DCP-funded severable Unit of Work for the CIPL lab (currently part of NCI Operational Task Order 75N91020F00003).