|
Cartilaginous exostosis
|
0.100 |
GeneticVariation
|
disease |
BEFREE |
This report shows that germline mutations of EXT2 can result, not only in the development of multiple benign osteochondromas, but also in the development of isolated malignant cartilaginous tumors including central tumors, and that the presence of germline EXT2 mutation should be considered in patients suspected to have an inherited predisposition to chondrosarcoma, even in the absence of MO.
|
27636706 |
2017 |
|
Cartilaginous exostosis
|
0.100 |
GeneticVariation
|
disease |
BEFREE |
Direct sequencing from DNA extracted from different sites of two tumor samples (a small rapidly growing osteochondroma and a giant peripheral secondary chondrosarcoma, each located at different chondrocostal junctions) revealed the loss of the germline EXT2 mutation.
|
25744876 |
2015 |
|
Cartilaginous exostosis
|
0.100 |
Biomarker
|
disease |
BEFREE |
Hereditary multiple exostoses patients carry heterozygous mutations in the heparan sulfate (HS)-synthesizing enzymes EXT1 or EXT2, but studies suggest that EXT haploinsufficiency and ensuing partial HS deficiency are insufficient for exostosis formation.
|
25863260 |
2015 |
|
Cartilaginous exostosis
|
0.100 |
GeneticVariation
|
disease |
BEFREE |
Here, employing a composite pipeline method derived from various inference-based programs, we have characterized 26 deletion CNVs [including three novel pathogenic CNVs involving an autosomal gene (EXT2) causing hereditary osteochondromas and an X-linked gene (CLCN5) causing Dent disease, as well as 23 CNVs previously identified by inference from a cohort of Canadian autism spectrum disorder families] to the single-base-pair level of accuracy from whole-genome sequencing data.
|
25792359 |
2015 |
|
Cartilaginous exostosis
|
0.100 |
GeneticVariation
|
disease |
BEFREE |
We report using a targeted-tiling-resolution oligo-array-CGH (array comparative genomic hybridization) that homozygous deletions of EXT1 or EXT2 are much less frequently detected (2/17, 12%) in sporadic secondary peripheral chondrosarcomas than expected based on the assumption that they originate in sporadic osteochondromas, in which homozygous inactivation of EXT1 is found in ~80% of our cases.
|
21804604 |
2012 |
|
Cartilaginous exostosis
|
0.100 |
GeneticVariation
|
disease |
BEFREE |
Here, we described that homozygous mutations in EXT1/EXT2, which are causative for osteochondroma formation, are likely to affect terminal chondrocyte differentiation and vascularisation in the osteocartilaginous interface.
|
22116208 |
2012 |
|
Cartilaginous exostosis
|
0.100 |
Biomarker
|
disease |
BEFREE |
Previously, we have used zebrafish which harbour mutations in ext2 as a model for MO and shown that ext2⁻/⁻ fish have skeletal defects that resemble those seen in osteochondromas.
|
22253766 |
2012 |
|
Cartilaginous exostosis
|
0.100 |
Biomarker
|
disease |
BEFREE |
EXT2-positive multiple hereditary osteochondromas with some features suggestive of metachondromatosis.
|
21892728 |
2012 |
|
Cartilaginous exostosis
|
0.100 |
GeneticVariation
|
disease |
BEFREE |
We describe the genetic examination of three secondary peripheral chondrosarcomas that had arisen synchronously from osteochondromas in a patient with MO by chromosome banding, high resolution chromosomal comparative genomic hybridization, and mutation analysis of the EXT1 and EXT2 genes.
|
22285020 |
2011 |
|
Cartilaginous exostosis
|
0.100 |
Biomarker
|
disease |
BEFREE |
Hampering elucidation of the pathogenic mechanism of MHE, both Ext1(+/-) and Ext2(+/-) heterozygous mutant mice, which mimic the genetic status of human MHE, are highly resistant to osteochondroma formation, especially in long bones.
|
20534475 |
2010 |
|
Cartilaginous exostosis
|
0.100 |
GeneticVariation
|
disease |
BEFREE |
Although both benign conditions have been linked to defects in EXT1 or EXT2 genes, contradictory reports are present in the literature regarding the requirement of their biallelic inactivation for osteochondroma development.
|
20418910 |
2010 |
|
Cartilaginous exostosis
|
0.100 |
AlteredExpression
|
disease |
BEFREE |
Reduced EXT1 or EXT2 expression in osteochondromas is associated with disordered cellular distribution of HSPGs, resulting in defective endochondral ossification which is likely to be involved in the formation of osteochondromas.
|
18853760 |
2008 |
|
Cartilaginous exostosis
|
0.100 |
AlteredExpression
|
disease |
BEFREE |
We investigated the expression of EXT1 and EXT2 (quantitative RT-PCR) and of different HSPGs (immunohistochemistry) in solitary and hereditary osteochondromas and in cases with malignant progression to secondary peripheral chondrosarcoma, in relation to possible mutations and promoter methylation.
|
17226760 |
2007 |
|
Cartilaginous exostosis
|
0.100 |
GeneticVariation
|
disease |
BEFREE |
Three different exostosis (EXT) loci on chromosomes 8q (exostosin 1, EXT1), 11p (exostosin 2, EXT2) and 19p (exostosin 3, EXT3) have been reported.
|
16638657 |
2006 |
|
Cartilaginous exostosis
|
0.100 |
GeneticVariation
|
disease |
BEFREE |
Mutations in either exostosin 1 (EXT1) or exostosin 2 (EXT2) gene cause the HME syndrome and also some isolated osteochondromas.
|
16026543 |
2005 |
|
Cartilaginous exostosis
|
0.100 |
Biomarker
|
disease |
BEFREE |
To evaluate promoter methylation (which is an epigenetic gene silencing mechanism) of EXT1 and EXT2, we performed methylation-specific polymerase chain reaction (PCR) for 20 chondrosarcoma cases (12 primary, 3 secondary to osteochondroma, 2 secondary to enchondromatosis, 2 extraskeletal ordinary, and 1 clear cell) and in five cell lines.
|
15796962 |
2005 |
|
Cartilaginous exostosis
|
0.100 |
Biomarker
|
disease |
BEFREE |
This provides limited support for the two-hit hypothesis involving the EXT1 and EXT2 genes for the development of an exostosis.
|
12239711 |
2002 |
|
Cartilaginous exostosis
|
0.100 |
Biomarker
|
disease |
BEFREE |
Among the four loci, the exostosis type 1 gene (EXT1) and type 2 gene (EXT2) have been cloned.
|
11170095 |
2001 |
|
Cartilaginous exostosis
|
0.100 |
GeneticVariation
|
disease |
BEFREE |
In this study, we have characterized exostosis chondrocytes from three patients with HME (one with EXT1 and two with EXT2 germline mutations) and from one individual with a non-HME, isolated exostosis.
|
10750558 |
2000 |
|
Cartilaginous exostosis
|
0.100 |
GeneticVariation
|
disease |
BEFREE |
EXT1- and EXT2-mutation analysis was performed in a total of 34 sporadic and hereditary osteochondromas and secondary peripheral chondrosarcomas.
|
10441575 |
1999 |
|
Cartilaginous exostosis
|
0.100 |
Biomarker
|
disease |
BEFREE |
These findings: 1) confirm previous observations of 8q24.1 karyotypic anomalies in sporadic osteochondroma, 2) reveal the presence of somatic chromosomal anomalies in hereditary osteochondromata, 3) suggest that similar to hereditary lesions, sporadic osteochondromas also are genetically heterogeneic (involvement of both 8q24.1 and 11p11-12), and 4) support the hypothesis that loss or mutation of EXT1 and EXT2, two putative tumor suppressor genes, may be important in the pathogenesis of sporadic as well as hereditary osteochondromata.
|
9576285 |
1998 |