Genetic alterations of protein-o-mannosyltransferase-1 in glioneuronal and glial brain tumors with subarachnoid spread

Neuropathology. 2009 Apr;29(2):116-24. doi: 10.1111/j.1440-1789.2008.00954.x. Epub 2008 Jul 20.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Brain Neoplasms / enzymology
  • Brain Neoplasms / genetics*
  • Brain Neoplasms / pathology
  • Child
  • Child, Preschool
  • Female
  • Glioma / enzymology
  • Glioma / genetics*
  • Glioma / pathology
  • Humans
  • Male
  • Mannosyltransferases / genetics*
  • Microdissection
  • Middle Aged
  • Mutation, Missense
  • Polymerase Chain Reaction
  • Polymorphism, Genetic
  • Sequence Analysis, DNA
  • Subarachnoid Space
  • Young Adult


  • Mannosyltransferases
  • protein O-mannosyltransferase