Despite the major findings, one limitation of the present study lies in the preselection of a panel of known cancer genes, and known genes related to CCR carcinogenesis were not included in the analysis, such as SMAD4 (altered in 11.6–12.9% of CRC), TTN (35.7–48.1%) and SYNE1 (21.0–48.1%)7,15,17. The gene discussed is SMAD4; the disease is cancer.