GEOapplication/xmlftp://ftp.ncbi.nlm.nih.gov/geo/series/GSE309nnn/GSE309783/primaryOK200Methylation profilingHomo sapiensMethylation profiling by high throughput sequencinghttps://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE309783GEOGSEfalseExercise-associated epigenetic remodeling and TCR repertoire dynamicsin Lynch Syndrome carriers (RRBS)Lynch Syndrome (LS) carriers are at elevated cancer risk. Recent data suggest exercise as a non-pharmacologic preventive strategy, yet the epigenetic and immunological mechanisms underlying its protective effects in this population remain unclear. Here, we perform integrative multi-omics profiling of DNA methylation, gene expression, and the T cell receptor (TCR) repertoire in LS carriers participating in a 52-week aerobic cycling intervention. We identify compartment-specific DNA methylation changes, including innate immune activation in cfDNA and oncogenic pathway repression in tissue. Transcriptomic integration highlights ISL1 as a key exercise-repressed gene and FLCN as a CRC-associated methylation target. TCR analysis reveals increased systemic repertoire diversity and tissue-specific clonal convergence, thus suggesting antigen-driven recruitment. These findings uncover epigenetic and immune remodeling as potential mechanisms of exercise-mediated protection in LS.2026/08/03GSE309783GSM9279042GSM9279043GSM9279044GSM9279045GSM9279046GSM927904721290309783Homo sapiens[42701426]