SMAD4 and adenoma: By comparing the mutation signatures of tubular adenomas, villous adenomas and FAP-CRC, we found that adenomas exhibited lower mutational rates than FAP-CRC and recurrent alterations were observed in well-known chromosomal instability (CIN) genes (APC, RAS, SMAD4 and TP53) and DNA damage repair genes (SUZ12, KMT2C, BCLAF1, RUNX1, and ARID1B) in the adenomas, suggesting the presence of genomic instability.