SMAD4, SMAD family member 4, 4089

N. diseases: 575; N. variants: 144
Source: ALL
Disease Score gda Association Type Type Original DB Sentence supporting the association PMID PMID Year
CUI: C0009402
Disease: Colorectal Carcinoma
Colorectal Carcinoma
0.700 GeneticVariation disease BEFREE Four hundred two patients (89.3%) had MMR-proficient tumors, and 32 patients (8%) had at least 1 gene mutation: 9 had mutations in high-penetrance CRC genes (5, APC; 1, APC/PMS2; 2, biallelic MUTYH; 1, SMAD4); 13 patients had mutations in high- or moderate-penetrance genes not traditionally associated with CRC (3, ATM; 1, ATM/CHEK2; 2, BRCA1; 4, BRCA2; 1, CDKN2A; 2, PALB2); 10 patients had mutations in low-penetrance CRC genes (3, APC c.3920T>A, p.I1307K; 7, monoallelic MUTYH). 27978560 2017
CUI: C0009402
Disease: Colorectal Carcinoma
Colorectal Carcinoma
0.700 GeneticVariation disease UNIPROT
CUI: C0009402
Disease: Colorectal Carcinoma
Colorectal Carcinoma
0.700 GeneticVariation disease BEFREE Among 734 patients with CRC, 90 (12%) had SMAD4 mutations according to hotspot testing. 28267766 2017
CUI: C0009402
Disease: Colorectal Carcinoma
Colorectal Carcinoma
0.700 GeneticVariation disease BEFREE Colorectal cancers (CRCs) frequently harbor somatic mutations in the pathway members TGFBR2 and SMAD4, but to what extent mutations in SMAD2 or SMAD3 contribute to tumorigenesis is unclear. 23139211 2013
CUI: C0009402
Disease: Colorectal Carcinoma
Colorectal Carcinoma
0.700 GeneticVariation disease BEFREE These results indicate that whereas Smad4 point mutations are prevalent in pancreatic carcinoma, they are infrequent in early stages (I-III) of colorectal cancer. 12569386 2003
CUI: C0009402
Disease: Colorectal Carcinoma
Colorectal Carcinoma
0.700 GeneticVariation disease BEFREE RT-PCR sequencing analysis of the HL60 Smad5 remaining allele ruled out the functional inactivation of the gene analogous to that occurring in the Smad5 homologs DPC4 and Smad2 in cases of pancreatic and colorectal cancers. 9264367 1997
CUI: C0009402
Disease: Colorectal Carcinoma
Colorectal Carcinoma
0.700 GeneticVariation disease BEFREE A transducer of TGF-beta signaling known as Mothers against decapentaplegic homologue 4 (Smad4) is a known tumor suppressor found on chromosome 18q21.1 and is typically inactivated by deletion or mutation in pancreatic and colorectal cancers. 18213629 2008
CUI: C0009402
Disease: Colorectal Carcinoma
Colorectal Carcinoma
0.700 GeneticVariation disease BEFREE Seven significantly mutated genes, including four reported (APC, TP53, KRAS and SMAD4) and three novel recurrently mutated genes (CDH10, FAT4 and DOCK2), exhibited high mutation prevalence (6-14% for novel cancer genes) and higher-than-expected number of non-silent mutations in our CRC cohort. 24951259 2015
CUI: C0009402
Disease: Colorectal Carcinoma
Colorectal Carcinoma
0.700 GeneticVariation disease BEFREE The aim of this study was to evaluate the clinicopathological characteristics and clinical significance of SMAD4 alteration detected with NGS in CRC. 30636020 2019
CUI: C0009402
Disease: Colorectal Carcinoma
Colorectal Carcinoma
0.700 GeneticVariation disease BEFREE Even in combination with changes in SMAD-4, the observed frequency was not sufficient to account for all 18q21 deletions in colorectal cancers. 9820171 1998
CUI: C0009402
Disease: Colorectal Carcinoma
Colorectal Carcinoma
0.700 GeneticVariation disease BEFREE GTF2IRD1 downregulated the expression of the gene encoding transforming growth factor β receptor 2 (TGFβR2), a tumor-suppressor gene in Smad4-mutated CRC. 31758608 2020
CUI: C0009402
Disease: Colorectal Carcinoma
Colorectal Carcinoma
0.700 GeneticVariation disease BEFREE Next, the prognostic value of SMAD4 mutation was validated in a separate cohort of patients with synchronous stage IV CRC who underwent systemic therapy alone. 29551247 2018
CUI: C0009402
Disease: Colorectal Carcinoma
Colorectal Carcinoma
0.700 GeneticVariation disease BEFREE The deleted in pancreatic cancer locus 4 (DPC4)/SMAD4 tumor suppressor gene is frequently inactivated in pancreatic (approximately 55%) and colorectal cancers (approximately 30%). 19276868 2009
CUI: C0009402
Disease: Colorectal Carcinoma
Colorectal Carcinoma
0.700 GeneticVariation disease BEFREE Other members of the SMAD family are excellent candidates for JPS, especially SMAD2 (which, like SMAD4, is mutated somatically in colorectal cancers), SMAD3 (which causes colorectal cancer when "knocked out" in mice), SMAD5, and SMAD1. 10446110 1999
CUI: C0009402
Disease: Colorectal Carcinoma
Colorectal Carcinoma
0.700 GeneticVariation disease BEFREE Two missense mutations in the C-terminal domain of Smad4, D351H (Asp351-->His) and D537Y (Asp537-->Tyr), have been described recently in the human colorectal cancer cell lines CACO-2 and SW948 respectively [Woodford-Richens, Rowan, Gorman, Halford, Bicknell, Wasan, Roylance, Bodmer and Tomlinson (2001) Proc.Natl.Acad.Sci.U.S.A. 98, 9719-9723]. 14715079 2004
CUI: C0009402
Disease: Colorectal Carcinoma
Colorectal Carcinoma
0.700 GeneticVariation disease BEFREE In patients with colorectal cancer (CRC), mutations or reduced levels of Smad4 have been correlated with reduced survival. 19909744 2010
CUI: C0009402
Disease: Colorectal Carcinoma
Colorectal Carcinoma
0.700 GeneticVariation disease BEFREE Correction: Association of SMAD4 mutation with patient demographics, tumor characteristics, and clinical outcomes in colorectal cancer. 28545046 2017
CUI: C0009402
Disease: Colorectal Carcinoma
Colorectal Carcinoma
0.700 GeneticVariation disease BEFREE Following the definition of SMAD4 deletion as a negative predictive marker for chemotherapy benefit in patients with CRC, we aimed to evaluate the clinical relevance of the deletion of other SMAD genes clustered in this region: SMAD2 and SMAD7 in 264 CRC biopsies from a previous clinical study. 12584741 2003
CUI: C0009402
Disease: Colorectal Carcinoma
Colorectal Carcinoma
0.700 GeneticVariation disease BEFREE These data suggest that DPC4 is rarely if ever mutated during prostatic oncogenesis, whereas inactivation of this gene may contribute to the genesis of a subset of colorectal carcinomas. 9285566 1997
CUI: C0009402
Disease: Colorectal Carcinoma
Colorectal Carcinoma
0.700 GeneticVariation disease BEFREE This approach classified CRC into two major groups consistent with previous classification systems: (1) ∼16 % hypermutated cancers with either microsatellite instability (MSI) due to defective mismatch repair (∼13 %) or ultramutated cancers with DNA polymerase epsilon proofreading mutations (∼3 %); and (2) ∼84 % non-hypermutated, microsatellite stable (MSS) cancers with a high frequency of DNA somatic copy number alterations, which showed common mutations in APC, TP53, KRAS, SMAD4, and PIK3CA. 27325016 2016
CUI: C0009402
Disease: Colorectal Carcinoma
Colorectal Carcinoma
0.700 GeneticVariation disease BEFREE The frequency of genomic alterations seen in SBA demonstrated distinct differences in comparison with either colorectal cancer (APC: 26.8% [85 of 317] vs 75.9% [4823 of 6353], P < .001; and CDKN2A: 14.5% [46 of 317] vs 2.6% [165 of 6353], P < .001) or gastric carcinoma (KRAS: 53.6% [170 of 317] vs 14.2% [126 of 889], P < .001; APC: 26.8% [85 of 317] vs 7.8% [69 of 889], P < .001; and SMAD4: 17.4% [55 of 317] vs 5.2% [46 of 889], P < .001). 28617917 2017
CUI: C0009402
Disease: Colorectal Carcinoma
Colorectal Carcinoma
0.700 GeneticVariation disease BEFREE Most of the approximately 13 high-penetrance genes that predispose to CRC primarily predispose to colorectal polyps, and each gene is associated with a specific type of polyp, whether conventional adenomas (APC, MUTYH, POLE, POLD1, NTHL1), juvenile polyps (SMAD4, BMPR1A), Peutz-Jeghers hamartomas (LKB1/STK11) and mixed polyps of serrated and juvenile types (GREM1). 26169059 2015
CUI: C0009402
Disease: Colorectal Carcinoma
Colorectal Carcinoma
0.700 GeneticVariation disease BEFREE The purpose of present study was to investigate the methylation status of the promoter region in five genes (mothers against decapentaplegic homolog 4, fragile histidine triad protein, death-associated protein kinase 1, adenomatous polyposis coli (APC), and E-cadherin), which are known to be involved in the pathogenesis of colorectal cancer (CRC) and its clinicopathological significance. 22990173 2013
CUI: C0009402
Disease: Colorectal Carcinoma
Colorectal Carcinoma
0.700 GeneticVariation disease BEFREE We investigated the prevalence of DPC4 loss of heterozygosity in sporadic colorectal cancer. 11357936 2001
CUI: C0009402
Disease: Colorectal Carcinoma
Colorectal Carcinoma
0.700 GeneticVariation disease BEFREE Higher frequency of Smad4 gene mutation in human colorectal cancer with distant metastasis. 10340381 1999