WCMC logo
PMKB
  • WCMC logoPMKB
  • Genes
  • Variants
  • Interpretations
  • Tumor Types
  • Primary Sites
  • Activity
  • Login
SMAD4
  • Information
  • View History
  • Pending Review
Interpretation 2311
Tier 2
SMAD4
Variants
SMAD4 any nonsense
Primary Sites
Small Intestine
Tumor Types
Adenocarcinoma
Interpretation

SMAD4 is a transcription factor that functions as a critical effector in the transforming growth factor beta (TGFss) signal pathway that controls cellular proliferation, differentiation and tissue homeostasis. The TGFss pathway suppresses tumorigenesis in premalignant states and promotes invasiveness and metastasis during cancer progression. Germline mutations in SMAD4 have been associated with juvenile polyposis syndrome (JPS). Somatic alterations in SMAD4 are in multiple tumor types, including colon and lung adenocarcinoma. SMAD4 inactivation by allelic deletion or mutation mainly occurs in late stage pancreatic ductal adenocarcinoma and is associated with poorer prognosis. SMAD4 loss increased resistance to the chemotherapeutic agent 5'-fluorouracil. The identified deletion is not characterized but is present at a site of frequent mutations and is potentially oncogenic. The role of SMAD4 variants in small intestinal adenocarcinomas need further characterization. Clinical correlation is recommended.

Citations
  1. Massague J. TGFb signalling in context. Nat Rev Mol Cell Biol. 2012 Oct;13(10):616-30. doi: 10.1038/nrm3434. Epub 2012 Sep 20. Review. PubMed PMID: 22992590; PubMed Central
  2. Massague J. TGFbeta in Cancer. Cell. 2008 Jul 25;134(2):215-30. doi: 10.1016/j.cell.2008.07.001. Review.
  3. Howe JR, Ringold JC, Summers RW, Mitros FA, Nishimura DY, Stone EM. A gene for familial juvenile polyposis maps to chromosome 18q21.1. Am J Hum Genet. 1998 May;62(5):1129-36.
  4. Fukushige S, Furukawa T, Satoh K, Sunamura M, Kobari M, Koizumi M, Horii A. Loss of chromosome 18q is an early event in pancreatic ductal tumorigenesis. Cancer Res. 1998 Oct 1;58(19):4222-6.
  5. Thiagalingam S, Lengauer C, Leach FS, Schutte M, Hahn SA, Overhauser J, Willson JK, Markowitz S, Hamilton SR, Kern SE, Kinzler KW, Vogelstein B. Evaluation of candidate tumour suppressor genes on chromosome 18 in colorectal cancers. Nat Genet. 1996 Jul;13(3):343-6.
  6. Hahn SA, Schutte M, Hoque AT, Moskaluk CA, da Costa LT, Rozenblum E, Weinstein
  7. CL, Fischer A, Yeo CJ, Hruban RH, Kern SE. DPC4, a candidate tumor suppressor gene at human chromosome 18q21.1. Science. 1996 Jan 19;271(5247):350-3.
  8. Fleming NI, Jorissen RN, Mouradov D, Christie M, Sakthianandeswaren A, Palmieri M, Day F, Li S, Tsui C, Lipton L, Desai J, Jones IT, McLaughlin S, Ward RL, Hawkins NJ, Ruszkiewicz AR, Moore J, Zhu HJ, Mariadason JM, Burgess AW, Busam D, Zhao Q, Strausberg RL, Gibbs P, Sieber OM. SMAD2, SMAD3 and SMAD4 mutations in colorectal cancer. Cancer Res. 2013 Jan 15;73(2):725-35.
  9. Bian C, Li Z, Xu Y, Wang J, Xu L, Shen H. Clinical outcome and expression of mutant P53, P16, and Smad4 in lung adenocarcinoma: a prospective study. World J Surg Oncol. 2015 Mar 28;13:128.
  10. Chen et al. SMAD4 Loss triggers the phenotypic changes of pancreatic ductal adenocarcinoma cells. BMC Cancer 2014, 14:181.
Last updated: 2019-01-22 18:42:56 UTC
PMKB Bot
  • Genes
  • Variants
  • Interpretations
  • Tumor Types
  • Primary Sites
  • Activity

Disclaimer: You assume full responsibility for all risks associated with using this PMKB website. The Englander Institute for Precision Medicine at Weill Cornell Medicine makes no guarantee of the comprehensiveness, reliability or accuracy of the information on this website and assumes no responsibility for errors in the information associated with this web site. Healthcare providers and patients must integrate all clinical and laboratory findings as well as information from a variety of sources before deciding on appropriate clinical care options.


When using PMKB, please cite: Huang et al., JAMIA 2017


HELP
User Guide
Video Tutorial
INFO
About
Latest
API
Twitter
CONTACT US
Contact

Englander Institute for Precision Medicine
© Weill Cornell Medicine | Version 1.7.2Privacy PolicyTerms of use