| Written | 2000-01 | Judith VMG Bovée |
| Afdeling Pathologie, Leids Universitair Medisch Centrum, Postbus 9600, L1-Q, 2300 RC Leiden, the Netherlands | ||
| Updated | 2002-03 | Judith VMG Bovée |
| Afdeling Pathologie, Leids Universitair Medisch Centrum, Postbus 9600, L1-Q, 2300 RC Leiden, the Netherlands |
| Identity |
| Alias_names | LGCR |
| LGS | |
| Langer-Giedion syndrome chromosome region | |
| exostoses (multiple) 1 | |
| exostosin 1 | |
| Alias_symbol (synonym) | ttv |
| Other alias | |
| HGNC (Hugo) | EXT1 |
| LocusID (NCBI) | 2131 |
| Atlas_Id | 212 |
| Location | 8q24.11 [Link to chromosome band 8q24] |
| Location_base_pair | Starts at 117799365 and ends at 118111819 bp from pter ( according to hg19-Feb_2009) [Mapping EXT1.png] |
 | |
| Probe(s) - Courtesy Mariano Rocchi, Resources for Molecular Cytogenetics | |
| Fusion genes (updated 2016) | ADGRB1 (8q24.3) / EXT1 (8q24.11) | DSCAM (21q22.2) / EXT1 (8q24.11) | EEF1A1 (6q13) / EXT1 (8q24.11) |
| EXT1 (8q24.11) / CLUL1 (18p11.32) | EXT1 (8q24.11) / DCTN6 (8p12) | EXT1 (8q24.11) / EXT1 (8q24.11) | |
| EXT1 (8q24.11) / FAM155A (13q33.3) | EXT1 (8q24.11) / FAM177A1 (14q13.2) | EXT1 (8q24.11) / OC90 (8q24.22) | |
| EXT1 (8q24.11) / RSF1 (11q14.1) | EXT1 (8q24.11) / SAMD12 (8q24.12) | EXT1 (8q24.11) / WDYHV1 (8q24.13) | |
| LRRC6 (8q24.22) / EXT1 (8q24.11) | RAB28 (4p15.33) / EXT1 (8q24.11) | RAD21 (8q24.11) / EXT1 (8q24.11) | |
| DNA/RNA |
 | |
| Description | 11 exons, spans approximately 350 kb of genomic DNA |
| Transcription | 3.4 kb |
| Protein |
| Description | 746 amino acids, 86.304 kDa |
| Expression | mRNA is ubiquitously expressed (also in chondrocytes), highest level of expression in liver. |
| Localisation | endoplasmic reticulum |
| Function | a tumour suppressor function is suggested; EXT1 is an endoplasmic reticulum (ER) resident type II transmembrane glycoprotein whose expression in cells alters the synthesis and display of cell surface heparan sulfate, and EXT1 was suggested to be involved in chain polymerization of heparan sulphate; an EXT1 homologue in Drosophila melanogaster (tout-velu, Ttv) was demonstrated to be involved in heparan sulphate proteoglycan biosynthesis controlling diffusion of an important segment polarity protein called Hedgehog (Hh) |
| Homology | human EXT2, EXTL1, EXTL2 and EXTL3, mouse Ext1, Drosophila tout velu |
| Mutations |
| Germinal | germline mutations in EXT1 are causative for hereditary multiple exostoses, a genetically heterogeneous autosomal dominant disorder; mutations include nucleotide substitutions (54%), small deletions (27%) and small insertions (16%), of which the majority is predicted to result in a truncated or non-functional protein |
| Somatic | no somatic mutations were found in 34 sporadic and hereditary osteochondromas and secondary peripheral chondrosarcomas tested |
| Implicated in |
| Note | |
| Entity | hereditary multiple exostoses |
| Prognosis | the main complication in hereditary multiple exostoses is malignant transformation of an osteochondroma (exostosis) into chondrosarcoma, which is estimated to occur in 1-5% of the HME cases |
| Cytogenetics | clonal aberrations were found at band 8q24.1 in sporadic and hereditary osteochondromas using cytogenetic analysis; loss of heterozygosity was almost exclusively found at the EXT1 locus in 5 out of 14 osteochondromas |
| Oncogenesis | two patients with multiple osteochondromas demonstrated a germline mutation combined with loss of the remaining wild type allele in three osteochondromas, supporting the Knudson's two hit model for tumour suppressor genes in osteochondroma development; these results indicate that in cartilaginous cells of the growth plate inactivation of both copies of the EXT1-gene is required for osteochondroma formation in hereditary cases |
| Bibliography |
| Cloning of the putative tumour suppressor gene for hereditary multiple exostoses (EXT1). |
| Ahn J, Lüdecke HJ, Lindow S, Horton WA, Lee B, Wagner MJ, Horsthemke B, Wells DE |
| Nature genetics. 1995 ; 11 (2) : 137-143. |
| PMID 7550340 |
| Tout-velu is a Drosophila homologue of the putative tumour suppressor EXT-1 and is needed for Hh diffusion. |
| Bellaiche Y, The I, Perrimon N |
| Nature. 1998 ; 394 (6688) : 85-88. |
| PMID 9665133 |
| Loss of heterozygosity and DNA ploidy point to a diverging genetic mechanism in the origin of peripheral and central chondrosarcoma. |
| Bovée JV, Cleton-Jansen AM, Kuipers-Dijkshoorn NJ, van den Broek LJ, Taminiau AH, Cornelisse CJ, Hogendoorn PC |
| Genes, chromosomes & cancer. 1999 ; 26 (3) : 237-246. |
| PMID 10502322 |
| Clonal karyotypic abnormalities of the hereditary multiple exostoses chromosomal loci 8q24.1 (EXT1) and 11p11-12 (EXT2) in patients with sporadic and hereditary osteochondromas. |
| Bridge JA, Nelson M, Orndal C, Bhatia P, Neff JR |
| Cancer. 1998 ; 82 (9) : 1657-1663. |
| PMID 9576285 |
| Genetic heterogeneity in families with hereditary multiple exostoses. |
| Cook A, Raskind W, Blanton SH, Pauli RM, Gregg RG, Francomano CA, Puffenberger E, Conrad EU, Schmale G, Schellenberg G |
| American journal of human genetics. 1993 ; 53 (1) : 71-79. |
| PMID 8317501 |
| Hereditary multiple exostosis and chondrosarcoma: linkage to chromosome II and loss of heterozygosity for EXT-linked markers on chromosomes II and 8. |
| Hecht JT, Hogue D, Strong LC, Hansen MF, Blanton SH, Wagner M |
| American journal of human genetics. 1995 ; 56 (5) : 1125-1131. |
| PMID 7726168 |
| The tumor suppressor EXT-like gene EXTL2 encodes an alpha1, 4-N-acetylhexosaminyltransferase that transfers N-acetylgalactosamine and N-acetylglucosamine to the common glycosaminoglycan-protein linkage region. The key enzyme for the chain initiation of heparan sulfate. |
| Kitagawa H, Shimakawa H, Sugahara K |
| The Journal of biological chemistry. 1999 ; 274 (20) : 13933-13937. |
| PMID 10318803 |
| Genomic organization and promoter structure of the human EXT1 gene. |
| Lüdecke HJ, Ahn J, Lin X, Hill A, Wagner MJ, Schomburg L, Horsthemke B, Wells DE |
| Genomics. 1997 ; 40 (2) : 351-354. |
| PMID 9119404 |
| Expression and functional analysis of mouse EXT1, a homolog of the human multiple exostoses type 1 gene. |
| Lin X, Gan L, Klein WH, Wells D |
| Biochemical and biophysical research communications. 1998 ; 248 (3) : 738-743. |
| PMID 9703997 |
| Isolation of the mouse cDNA homologous to the human EXT1 gene responsible for Hereditary Multiple Exostoses. |
| Lin X, Wells D |
| DNA sequence : the journal of DNA sequencing and mapping. 1997 ; 7 (3-4) : 199-202. |
| PMID 9254013 |
| The putative tumor suppressors EXT1 and EXT2 are glycosyltransferases required for the biosynthesis of heparan sulfate. |
| Lind T, Tufaro F, McCormick C, Lindahl U, Lidholt K |
| The Journal of biological chemistry. 1998 ; 273 (41) : 26265-26268. |
| PMID 9756849 |
| The murine Ext1 gene shows a high level of sequence similarity with its human homologue and is part of a conserved linkage group on chromosome 15. |
| Lohmann DR, Buiting K, Lüdecke HJ, Horsthemke B |
| Cytogenetics and cell genetics. 1997 ; 76 (3-4) : 164-166. |
| PMID 9186511 |
| The putative tumour suppressor EXT1 alters the expression of cell-surface heparan sulfate. |
| McCormick C, Leduc Y, Martindale D, Mattison K, Esford LE, Dyer AP, Tufaro F |
| Nature genetics. 1998 ; 19 (2) : 158-161. |
| PMID 9620772 |
| Loss of chromosome band 8q24 in sporadic osteocartilaginous exostoses. |
| Mertens F, Rydholm A, Kreicbergs A, Willén H, Jonsson K, Heim S, Mitelman F, Mandahl N |
| Genes, chromosomes & cancer. 1994 ; 9 (1) : 8-12. |
| PMID 7507706 |
| Loss of heterozygosity in chondrosarcomas for markers linked to hereditary multiple exostoses loci on chromosomes 8 and 11. |
| Raskind WH, Conrad EU, Chansky H, Matsushita M |
| American journal of human genetics. 1995 ; 56 (5) : 1132-1139. |
| PMID 7726169 |
| A direct interaction between EXT proteins and glycosyltransferases is defective in hereditary multiple exostoses. |
| Simmons AD, Musy MM, Lopes CS, Hwang LY, Yang YP, Lovett M |
| Human molecular genetics. 1999 ; 8 (12) : 2155-2164. |
| PMID 10545594 |
| Hedgehog movement is regulated through tout velu-dependent synthesis of a heparan sulfate proteoglycan. |
| The I, Bellaiche Y, Perrimon N |
| Molecular cell. 1999 ; 4 (4) : 633-639. |
| PMID 10549295 |
| Citation |
| This paper should be referenced as such : |
| Boée, JVMG |
| EXT1 (exostoses (multiple) 1) |
| Atlas Genet Cytogenet Oncol Haematol. 2002;6(3):184-185. |
| Free journal version : [ pdf ] [ DOI ] |
| On line version : http://AtlasGeneticsOncology.org/Genes/EXT1ID212.html |
| History of this paper: |
| Bovée, JVMG. EXT1 (exostoses (multiple) 1). Atlas Genet Cytogenet Oncol Haematol. 2000;4(1):3-4. |
| http://documents.irevues.inist.fr/bitstream/handle/2042/37575/01-2000-EXT1ID212.pdf |
| Other Solid tumors implicated (Data extracted from papers in the Atlas) [ 3 ] |
|
Bone tumors: an overview
Bone: Chondrosarcoma Bone: Osteochondroma |
| Other Cancer prone implicated (Data extracted from papers in the Atlas) [ 1 ] |
| Multiple osteochondromas (MO) |
| External links |
| REVIEW articles | automatic search in PubMed |
| Last year publications | automatic search in PubMed |
| © Atlas of Genetics and Cytogenetics in Oncology and Haematology | indexed on : Fri Jun 30 11:06:21 CEST 2017 |
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