SMAD4 (SMAD family member 4, also known as DPC4), is a gene that encodes the mothers against decapentaplegic homolog 4 protein, one of eight SMAD proteins in the human genome (PMID: 9759503). SMAD4 is a member of the TGF-β pathway, which plays a complex role in cancer development, progression, and metastasis (PMID: 16794634; PMID: 15774796; PMID: 18662538; PMID: 12821112). Mutations in SMAD4 are involved in several hereditary syndromes with cancer predisposition, including juvenile polyposis syndrome and hemorrhagic hereditary telangiectasia (HHT) syndrome. SMAD4 loss or mutation is also seen in pancreatic tumors and colorectal cancer (PMID: 15774796; PMID: 8553070; PMID: 10340381).
SMAD4 is altered in 4.38% of all cancers with colon adenocarcinoma, pancreatic adenocarcinoma, lung adenocarcinoma, colorectal adenocarcinoma, and rectal adenocarcinoma having the greatest prevalence of alterations .
The most common alterations in SMAD4 are SMAD4 Mutation (3.21%), SMAD4 Loss (0.70%), SMAD4 R361H (0.40%), SMAD4 R361C (0.26%), and SMAD4 R445* (0.08%) .
2. The UniProt Consortium. UniProt: a worldwide hub of protein knowledge. Nucleic Acids Research. 2019;47:D506-D515.
3. The AACR Project GENIE Consortium. AACR Project GENIE: powering precision medicine through an international consortium. Cancer Discovery. 2017;7(8):818-831. Dataset Version 8. This dataset does not represent the totality of the genetic landscape; see paper for more information.