SMAD3 and cancer: While inactivating mutations in SMAD3 were previously believed to be absent in all cancer types [14], a putative inactivating missense mutation (R373H) was found in the colorectal cancer cell line SNU-769A [15] as well as c.1009+1G > A and c.1178C > T (P393L) from the screening of 38 primary colorectal cancers [16] both localized to the MH2 domain.