PMID- 10441575
OWN - NLM
STAT- MEDLINE
DCOM- 19991004
LR  - 20220409
IS  - 0002-9297 (Print)
IS  - 0002-9297 (Linking)
VI  - 65
IP  - 3
DP  - 1999 Sep
TI  - EXT-mutation analysis and loss of heterozygosity in sporadic and hereditary
      osteochondromas and secondary chondrosarcomas.
PG  - 689-98
AB  - Osteochondromas occur as sporadic solitary lesions or as multiple lesions,
      characterizing the hereditary multiple exostoses syndrome (EXT). Approximately
      15% of all chondrosarcomas arise within the cartilaginous cap of an
      osteochondroma. EXT is genetically heterogeneous, and two genes, EXT1 and EXT2,
      located on 8q24 and 11p11-p12, respectively, have been cloned. It is still
      unclear whether osteochondroma is a developmental disorder or a true neoplasm.
      Furthermore, it is unclear whether inactivation of both alleles of an EXT gene,
      according to the tumor-suppressor model, is required for osteochondroma
      development, or whether a single EXT germline mutation acts in a dominant
      negative way. We therefore studied loss of heterozygosity and DNA ploidy in eight
      sporadic and six hereditary osteochondromas. EXT1- and EXT2-mutation analysis was
      performed in a total of 34 sporadic and hereditary osteochondromas and secondary 
      peripheral chondrosarcomas. We demonstrated osteochondroma to be a true neoplasm,
      since aneuploidy was found in 4 of 10 osteochondromas. Furthermore, LOH was
      almost exclusively found at the EXT1 locus in 5 of 14 osteochondromas. Four novel
      constitutional cDNA alterations were detected in exon 1 of EXT1. Two patients
      with multiple osteochondromas demonstrated a germline mutation combined with loss
      of the remaining wild-type allele in three osteochondromas, indicating that, in
      cartilaginous cells of the growth plate, inactivation of both copies of the EXT1 
      gene is required for osteochondroma formation in hereditary cases. In contrast,
      no somatic EXT1 cDNA alterations were found in sporadic osteochondromas. No
      mutations were found in the EXT2 gene.
FAU - Bovee, J V
AU  - Bovee JV
AD  - Departments of Pathology, Leiden University Medical Center, Leiden, The
      Netherlands. JBovee@Pat.azl.nl
FAU - Cleton-Jansen, A M
AU  - Cleton-Jansen AM
FAU - Wuyts, W
AU  - Wuyts W
FAU - Caethoven, G
AU  - Caethoven G
FAU - Taminiau, A H
AU  - Taminiau AH
FAU - Bakker, E
AU  - Bakker E
FAU - Van Hul, W
AU  - Van Hul W
FAU - Cornelisse, C J
AU  - Cornelisse CJ
FAU - Hogendoorn, P C
AU  - Hogendoorn PC
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Am J Hum Genet
JT  - American journal of human genetics
JID - 0370475
RN  - 0 (Codon)
RN  - 0 (Proteins)
RN  - EC 2.4.1.- (N-Acetylglucosaminyltransferases)
RN  - EC 2.4.1.224 (exostosin-1)
RN  - EC 2.4.1.224 (exostosin-2)
SB  - IM
MH  - Adolescent
MH  - Adult
MH  - Amino Acid Sequence
MH  - Base Sequence
MH  - Child
MH  - Chondrosarcoma/*genetics/secondary
MH  - Codon/genetics
MH  - DNA Mutational Analysis
MH  - Female
MH  - Flow Cytometry
MH  - Genes, Dominant/genetics
MH  - Germ-Line Mutation/genetics
MH  - Humans
MH  - Loss of Heterozygosity/*genetics
MH  - Male
MH  - Microsatellite Repeats/genetics
MH  - Middle Aged
MH  - Mutation/*genetics
MH  - *N-Acetylglucosaminyltransferases
MH  - Osteochondroma/*genetics
MH  - Ploidies
MH  - Polymorphism, Single-Stranded Conformational
MH  - Proteins/*genetics
PMC - PMC1377975
EDAT- 1999/08/12 10:00
MHDA- 2000/03/21 09:00
CRDT- 1999/08/12 10:00
PHST- 1999/08/12 10:00 [pubmed]
PHST- 2000/03/21 09:00 [medline]
PHST- 1999/08/12 10:00 [entrez]
AID - S0002-9297(07)62320-9 [pii]
AID - 10.1086/302532 [doi]
PST - ppublish
SO  - Am J Hum Genet. 1999 Sep;65(3):689-98. doi: 10.1086/302532.