|
Primary malignant neoplasm
|
0.100 |
GeneticVariation
|
group |
BEFREE |
DPC4/SMAD4 gene alterations in human cancer, and their functional implications.
|
10436786 |
1999 |
|
Primary malignant neoplasm
|
0.100 |
GeneticVariation
|
group |
BEFREE |
Juvenile polyposis syndrome (JPS) is a rare autosomal dominant disorder predisposing to gastrointestinal hamartomatous polyps and cancer with a pathogenic SMAD4 or BMPR1A germline mutation (1st-hit) being identified in about 40-50% of patients.
|
26171675 |
2015 |
|
Primary malignant neoplasm
|
0.100 |
GeneticVariation
|
group |
BEFREE |
Smad4 plays an important role in human physiology, and its mutations were found with high frequency in wide range of human cancer.
|
22109972 |
2012 |
|
Primary malignant neoplasm
|
0.100 |
GeneticVariation
|
group |
BEFREE |
We examined DPC4 mutation in 30 examples of three other types of gastrointestinal malignancy: 10 esophageal cancers, 10 gastric cancers and 10 colorectal cancers occurring in the preneoplastic condition, ulcerative colitis.
|
8957088 |
1996 |
|
Primary malignant neoplasm
|
0.100 |
GeneticVariation
|
group |
BEFREE |
No MSI(+) cancer showed loss of SMAD4 protein or SMAD4 mutation, and very few had allelic loss at SMAD4 or DCC, although many of these MSI(+) lines did carry TGFBIIR changes.
|
11481457 |
2001 |
|
Primary malignant neoplasm
|
0.100 |
GeneticVariation
|
group |
BEFREE |
Histological analysis of the PDXs and primary tumors revealed a conserved expression pattern of p53 and SMAD4; an exome single nucleotide polymorphism (SNP) array and Comprehensive Cancer Panel showed that PDXs retained over 94% of cancer-associated variants.
|
27613834 |
2016 |
|
Primary malignant neoplasm
|
0.100 |
GeneticVariation
|
group |
BEFREE |
In addition to the known cancer-related genes TP53 (mutated in 44.4% of cases), KRAS (16.7%) and SMAD4 (16.7%), we identified somatic mutations in 10 newly implicated genes in 14.8-3.7% of cases.
|
22561520 |
2012 |
|
Primary malignant neoplasm
|
0.100 |
GeneticVariation
|
group |
BEFREE |
These results suggest an important role for the SCFSkp2 complex in switching cancer mutants of Smad4 to undergo polyubiquitination-dependent degradation.
|
15314162 |
2004 |
|
Primary malignant neoplasm
|
0.100 |
GeneticVariation
|
group |
BEFREE |
Mutant SMAD4 PDAC increases tumor cell tension to modulate fibrosis and increase malignancy.
|
27150537 |
2016 |
|
Primary malignant neoplasm
|
0.100 |
GeneticVariation
|
group |
BEFREE |
Translational research aimed at investigating potential application of mononucleotide repeats -462T(15) and -4T(12) in SMAD4 gene promoter as molecular markers in cancer may also prove useful.
|
21036691 |
2011 |
|
Primary malignant neoplasm
|
0.100 |
GeneticVariation
|
group |
BEFREE |
This review lists SMAD4 mutations in various types of cancer and summarizes recent advances on SMAD4 with focuses on the function, signaling pathway, and the possibility of SMAD4 as a prognostic indicator.
|
29483830 |
2018 |
|
Primary malignant neoplasm
|
0.100 |
GeneticVariation
|
group |
BEFREE |
Inactivating mutations of the tumour suppressor genes TP53, CDKN2 and SMAD4 are also frequently observed and this constellation of genetic defects sets pancreatic cancer apart from other types of cancer, a feature which could have important implications for molecular diagnosis.
|
9438601 |
1997 |
|
Primary malignant neoplasm
|
0.100 |
GeneticVariation
|
group |
BEFREE |
The increased neoplastic risk may result from SMAD-4 mutations in the stromal component, which stimulate epithelial dysplasia and progression to invasive malignancy.
|
11352305 |
2001 |
|
Primary malignant neoplasm
|
0.100 |
GeneticVariation
|
group |
BEFREE |
Analysis of data from The Cancer Genome Atlas revealed that Smad4 mutation or homozygous loss was mutually exclusive with genomic alterations in DNA repair molecules.
|
28577946 |
2017 |
|
Primary malignant neoplasm
|
0.100 |
GeneticVariation
|
group |
BEFREE |
In the present study, we analyzed 15 human pancreatic cancer cell lines for genetic alterations of the K-ras, p53, p16, and SMAD4 genes, which are very frequent targets for mutation in pancreatic cancer; these cell lines are useful resources in cancer research.
|
11115575 |
2001 |
|
Primary malignant neoplasm
|
0.100 |
GeneticVariation
|
group |
BEFREE |
Findings on the role and potential significance of the K-ras codon 12 mutation and SMAD4 gene promoter variants in patients with endometrial carcinoma remain controversial, and their occurrence in this type of cancer should be further investigated.
|
22266936 |
2012 |
|
Primary malignant neoplasm
|
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 |
|
Primary malignant neoplasm
|
0.100 |
GeneticVariation
|
group |
BEFREE |
No patient was diagnosed with cancer in the BMPR1A group, whereas four men with a SMAD4 mutation developed gastrointestinal (3) or extraintestinal (1) cancer.
|
25389115 |
2015 |
|
Primary malignant neoplasm
|
0.100 |
Biomarker
|
group |
BEFREE |
Here, we present a review of the current state of the literature implicating the central Smad mediator, Smad4, in the development of cancer.
|
9862572 |
1998 |
|
Primary malignant neoplasm
|
0.100 |
Biomarker
|
group |
BEFREE |
Expression levels of Runx3 respond to and combine with Dpc4 status to coordinately regulate the balance between cancer cell division and dissemination.
|
26004068 |
2015 |
|
Primary malignant neoplasm
|
0.100 |
Biomarker
|
group |
BEFREE |
TGF-beta-induced nuclear localization of Smad2 and Smad3 in Smad4 null cancer cell lines.
|
12618756 |
2003 |
|
Primary malignant neoplasm
|
0.100 |
Biomarker
|
group |
BEFREE |
SMAD4 is a polypeptide with tumor suppressor function being investigated as a prognostic biomarker in Union Internationale Contre le Cancer stages II and III in previous studies, but its role as a prognostic marker in stage IV colorectal cancer (CRC) is still undefined.
|
21609932 |
2011 |
|
Primary malignant neoplasm
|
0.100 |
Biomarker
|
group |
BEFREE |
However, the mechanism by which SMAD4 antagonizes WNT/β-catenin signaling in cancer remains largely unknown.
|
25061104 |
2014 |
|
Primary malignant neoplasm
|
0.100 |
Biomarker
|
group |
BEFREE |
We showed that the absence of Smad4 alone did not trigger pancreas tumor formation; however, it increased the expression of an inactivated form of Pten, suggesting a role of Pten in preventing Smad4-/- cells from undergoing malignancy.
|
19901970 |
2010 |
|
Primary malignant neoplasm
|
0.100 |
Biomarker
|
group |
BEFREE |
Pancreatic ductal adenocarcinoma (PDAC) is an aggressive human malignancy in which the transforming growth factor beta (TGF-beta) signal transducer, Smad4, is commonly mutated or deleted.
|
16320109 |
2005 |