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 |
Colorectal Carcinoma
|
0.700 |
GeneticVariation
|
disease |
UNIPROT |
|
|
|
Colorectal Carcinoma
|
0.700 |
GeneticVariation
|
disease |
BEFREE |
Among 734 patients with CRC, 90 (12%) had SMAD4 mutations according to hotspot testing.
|
28267766 |
2017 |
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 |
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 |
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 |
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 |
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 |
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 |
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 |
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 |
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 |
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 |
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 |
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 |
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 |
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 |
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 |
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 |
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 |
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 |
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 |
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 |
Colorectal Carcinoma
|
0.700 |
GeneticVariation
|
disease |
BEFREE |
We investigated the prevalence of DPC4 loss of heterozygosity in sporadic colorectal cancer.
|
11357936 |
2001 |
Colorectal Carcinoma
|
0.700 |
GeneticVariation
|
disease |
BEFREE |
Higher frequency of Smad4 gene mutation in human colorectal cancer with distant metastasis.
|
10340381 |
1999 |