|
Colorectal Carcinoma
|
0.400 |
GeneticVariation
|
disease |
BEFREE |
Genetic mutations can occur in the precursors, and the combined prevalence of SMAD4, SMAD2, and SMAD3 mutations was seen in up to 50% of CRCs.
|
28601657 |
2017 |
|
Colorectal Carcinoma
|
0.400 |
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
|
0.400 |
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
|
0.400 |
GeneticVariation
|
disease |
BEFREE |
Ten gastric and 9 colorectal PDECs, 9 gastric WDECs, and 12 colorectal carcinomas (CRCs) were analyzed for loss of heterozygosity (LOH) at 11q13 (MEN1), 17p13.1 (p53), 3p14.2 (FHIT), 3p21.3 (RASSF1A), and 18q23 (DCC/DPC4/Smad2), and for immunohistochemical expression of p53, FHIT, Rb, and p16.
|
12973852 |
2003 |
|
Colorectal Carcinoma
|
0.400 |
GeneticVariation
|
disease |
UNIPROT |
|
|
|
|
Colorectal Carcinoma
|
0.400 |
GeneticVariation
|
disease |
BEFREE |
The MUTYH mutational signature reflecting persistent 8-oxoG:A mismatches occurs frequently in the APC, KRAS, PIK3CA, FAT4, TP53, FAT1, AMER1, KDM6A, SMAD4 and SMAD2 genes that are associated with CRC.
|
28551381 |
2017 |
|
Colorectal Carcinoma
|
0.400 |
GeneticVariation
|
disease |
BEFREE |
A similar invasive phenotype was obtained in cells expressing another inactivating mutation in Smad2 (Smad2.P445H) found in colorectal cancer.
|
10438456 |
1999 |
|
Colorectal Carcinoma
|
0.400 |
GeneticVariation
|
disease |
BEFREE |
By the PCR-SSCP method using these primers, we screened genomic DNA sequences of colorectal cancers for mutations of the Smad2 gene.
|
9635866 |
1998 |
|
Colorectal Carcinoma
|
0.400 |
GeneticVariation
|
disease |
BEFREE |
Furthermore, the analysis of the Cancer Genome Atlas data revealed that in CRC without microsatellite instability, overexpression of Myc and inactivation of Smads (including acquired mutations in SMAD2) are mutually exclusive, with odds ratio less than 0.1.
|
24627270 |
2014 |
|
Loeys-Dietz Syndrome
|
0.330 |
GeneticVariation
|
disease |
BEFREE |
CNC-, but not SHF-specific, deletion of Smad2 preserved aortic wall architecture and reduced aortic dilation in this mouse model of LDS.
|
30614814 |
2019 |
|
Liver carcinoma
|
0.300 |
GeneticVariation
|
disease |
BEFREE |
However, mechanisms as mutations in TGF-beta receptor II or Smad2 and 4 genes, frequently observed in other human cancers, have only rarely been observed in hepatocellular carcinomas.
|
11170302 |
2001 |
|
Liver carcinoma
|
0.300 |
GeneticVariation
|
disease |
BEFREE |
These results suggest that mutations of the TGFbetaRII, Smad2, and Smad4 genes are rare, and that genetic instability is uncommon in human hepatocellular carcinoma.
|
9863018 |
1999 |
|
Liver carcinoma
|
0.300 |
GeneticVariation
|
disease |
BEFREE |
Using the HepG2 hepatoma cells, we showed here that expression of Smad2.Q407R, a missense mutation found in human hepatocellular carcinoma, was less effective than expression of wild-type Smad2 in enhancing the ability of TGF-beta to induce transcription from the Mix.2 promoter.
|
12700238 |
2003 |
|
Liver carcinoma
|
0.300 |
GeneticVariation
|
disease |
BEFREE |
These results suggest that mutations of the hsMAD2, hBUB1 and hBUB3 genes are very rare in bladder tumors and that hsMAD2 alterations are also infrequent in soft-tissue sarcomas and hepatocellular carcinomas.
|
11400114 |
2001 |
|
Liver carcinoma
|
0.300 |
GeneticVariation
|
disease |
BEFREE |
We studied 35 HCC and non-tumour liver tissues for possible mutations in Smad2 and Smad4 genes.
|
10490821 |
1999 |
|
Liver carcinoma
|
0.300 |
GeneticVariation
|
disease |
BEFREE |
To investigate the involvement of autocrine TGF-beta signal in cell growth, PAI-1 and VEGF production of HCC, we made stable transfectants of human HCC line (HuH-7 cells) to express a mutant Smad2(3S-A), in which serine residues of SSXS motif were changed to alanine.
|
12700666 |
2003 |
|
Malignant Neoplasms
|
0.100 |
GeneticVariation
|
group |
BEFREE |
However, mechanisms as mutations in TGF-beta receptor II or Smad2 and 4 genes, frequently observed in other human cancers, have only rarely been observed in hepatocellular carcinomas.
|
11170302 |
2001 |
|
Malignant Neoplasms
|
0.100 |
GeneticVariation
|
group |
BEFREE |
The majority of Smad4 gene mutations in human cancer are missense, nonsense, and frameshift mutations at the mad homology 2 region (MH2), which interfere with the homo-oligomer formation of Smad4 protein and the hetero-oligomer formation between Smad4 and Smad2 proteins, resulting in disruption of TGFbeta signaling.
|
12821112 |
2003 |
|
Malignant Neoplasms
|
0.100 |
GeneticVariation
|
group |
BEFREE |
Furthermore, the analysis of the Cancer Genome Atlas data revealed that in CRC without microsatellite instability, overexpression of Myc and inactivation of Smads (including acquired mutations in SMAD2) are mutually exclusive, with odds ratio less than 0.1.
|
24627270 |
2014 |
|
Malignant neoplasm of stomach
|
0.100 |
GeneticVariation
|
disease |
BEFREE |
PCR-SSCP analysis of the entire coding region of Smad2 in 35 human sporadic gastric cancers and eight gastric cancer cell lines was performed using 11 sets of intron-based primers.
|
10073143 |
1999 |
|
Neoplasms
|
0.100 |
GeneticVariation
|
group |
BEFREE |
Compiled data for SMAD genes in each tumor show that the most common combination (26% of all the tumors) consists of the simultaneous deletions of SMAD2 and SMAD4 associated with normal diploidy or even duplication of SMAD7.
|
11391794 |
2001 |
|
Neoplasms
|
0.100 |
GeneticVariation
|
group |
BEFREE |
These results indicate that mutations of the hsMAD2 and hBUB1 genes are very rare and presumably play a very restricted role in tumor development of sporadic cancers.
|
10543255 |
1999 |
|
Neoplasms
|
0.100 |
GeneticVariation
|
group |
BEFREE |
In hepatocellular carcinomas, the potential role of TGF-beta signaling as a tumor suppressor pathway can be illustrated by the presence of mutations in genes encoding TGF-beta receptors or downstream components of this signaling such as Smad2.
|
12700238 |
2003 |
|
Neoplasms
|
0.100 |
GeneticVariation
|
group |
BEFREE |
The Skil mRNA level was associated with tumour stage (P = 0.03), and the Smad2/3/4 mRNA level with tumour grade (P = 0.03, P = 0.02, and P = 0.00, respectively).
|
21771027 |
2011 |
|
Neoplasms
|
0.100 |
GeneticVariation
|
group |
BEFREE |
Three tumours displayed somatic mutations; two in Smad4 (Asp332Gly and Cys401Arg) and one in Smad2 (Gln407Arg) genes.
|
10490821 |
1999 |