At the genomic level, germline mutations in homologous recombination repair and DNA damage checkpoint genes (BRCA1/2, ATM, CHEK2) interact synergistically with somatic epigenetic alterations such as KDM6A mutations and ERBB2 amplification, collectively disrupting chromatin regulation and genome stability to drive CRC development [84]. The gene discussed is KDM6A; the disease is colorectal carcinoma.