Source:http://linkedlifedata.com/resource/pubmed/id/18647264
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| Predicate | Object |
|---|---|
| rdf:type | |
| lifeskim:mentions | |
| pubmed:issue |
2
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| pubmed:dateCreated |
2009-4-1
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| pubmed:abstractText |
Leptomeningeal spread is a casual but conspicuous finding in both low- and high-grade gliomas. We hypothesized a compromised integrity of the glia limitans-basal lamina complex due to glycosylation defects by loss of protein-o-mannosyltransferase-1 (POMT1) activity, also a well-known feature in developmental brain disorders with leptomeningeal heterotopia. Hypothesizing it as analogous in gliomas, we have performed a comprehensive polymerase chain reaction-single strand conformation polymorphism (PCR-SSCP) analysis of the POMT1 gene in 41 brain tumor specimens. Each specimen was subjected to laser capture microdissection analyses to dissect: (i) subarachnoid tumor components; (ii) deeply localized tumor areas; and (iii) histologically unaffected CNS fragments. In addition, leukocyte DNA of healthy Caucasians served as controls (n = 100). Sequence alterations were found in exons 7, 9, 15 and 18. Exon 7 bore two sequence alterations, one 751C > T transition with amino acid exchange of arginine by tryptophane (Arg251Trp) (n = 12/41 in Tu vs n = 7/82 in Co) and a 752G > A transition with replacement of arginine by glutamine (Arg251Gln) (n = 3/41 in Tu vs n = 0/82 in Co) that were significantly increased in the tumor specimens compared to controls (P < 0.05). A 979G > A transition in exon 9 resulted in a valine to isoleucine switch (Val327Ile) (n = 6/40 in Tu vs n = 4/84 in Co). Individual specimens revealed a 1565G > A (Arg522Lys) transition in exon 15 and a 1922C > T (Ala641Val) transition in exon 18. Two gangliogliomas only revealed sequence alterations in the superficial area but not in intraparenchymal and adjacent control specimens. We conclude that a significant increase of POMT1 missense mutations may indicate a functional role in neoplastic conditions in individual tumors. Future studies will be important to evaluate a functional impact of POMT1 alterations in human brain tumors.
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| pubmed:language |
eng
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| pubmed:journal | |
| pubmed:citationSubset |
IM
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| pubmed:chemical | |
| pubmed:status |
MEDLINE
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| pubmed:month |
Apr
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| pubmed:issn |
1440-1789
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| pubmed:author | |
| pubmed:issnType |
Electronic
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| pubmed:volume |
29
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| pubmed:owner |
NLM
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| pubmed:authorsComplete |
Y
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| pubmed:pagination |
116-24
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| pubmed:meshHeading |
pubmed-meshheading:18647264-Adolescent,
pubmed-meshheading:18647264-Adult,
pubmed-meshheading:18647264-Aged,
pubmed-meshheading:18647264-Brain Neoplasms,
pubmed-meshheading:18647264-Child,
pubmed-meshheading:18647264-Child, Preschool,
pubmed-meshheading:18647264-Female,
pubmed-meshheading:18647264-Glioma,
pubmed-meshheading:18647264-Humans,
pubmed-meshheading:18647264-Male,
pubmed-meshheading:18647264-Mannosyltransferases,
pubmed-meshheading:18647264-Microdissection,
pubmed-meshheading:18647264-Middle Aged,
pubmed-meshheading:18647264-Mutation, Missense,
pubmed-meshheading:18647264-Polymerase Chain Reaction,
pubmed-meshheading:18647264-Polymorphism, Genetic,
pubmed-meshheading:18647264-Sequence Analysis, DNA,
pubmed-meshheading:18647264-Subarachnoid Space,
pubmed-meshheading:18647264-Young Adult
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| pubmed:year |
2009
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| pubmed:articleTitle |
Genetic alterations of protein-o-mannosyltransferase-1 in glioneuronal and glial brain tumors with subarachnoid spread.
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| pubmed:affiliation |
Department of Neuropathology, University of Bonn Medical Center, Bonn, Germany. jsnoei@uni-bonn.de
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| pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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