Analysis of the PTEN gene in human meningiomas.
Previous observations demonstrated that the neurofibromatosis type 2 gene (NF2) plays an important role in the pathogenesis of the transitional, fibroblastic and malignant variants of human meningiomas. No specific genes have been associated with the pathogenesis of meningothelial meningiomas and with the progression to anaplastic meningiomas. However, allelic losses on chromosomal arms 1p, 10q and 14q have been implicated in the process of malignant progression. Recently, PTEN (phosphatase and tensin homolog deleted on chromosome ten) also termed MMAC1 (mutated in multiple advanced cancers 1) or TEP1 (TGF--regulated and epithelial cell-enriched phosphatase), emerged as a candidate gene on chromosome 10q23.3. Initial studies revealed mutations of PTEN in limited series of glioblastomas, breast, kidney and prostate carcinomas mainly as cell lines. In order to evaluate the involvement of PTEN in the development of meningiomas, we have analysed the entire coding sequence of the gene in a series of 55 meningiomas (WHO grade I). 10 atypical meningiomas (WHO grade II) and 10 anaplastic meningiomas (WHO grade III). No PTEN mutations were seen in the WHO grade I meningiomas. However, one of the anaplastic meningiomas carried a somatic mutation. In addition, all tumours were examined for the presence of homozygous deletions of PTEN but these were not detected in any of the meningiomas. Our data suggest that mutations in PTEN are not involved in the formation of low grade meningiomas, but may contribute to malignant progression in a fraction of anaplastic meningiomas.
Peters
N
N
Department of Neuropathology, University of Bonn Medical Centre, Germany.
Wellenreuther
R
R
Rollbrocker
B
B
Hayashi
Y
Y
Meyer-Puttlitz
B
B
Duerr
E M
EM
Lenartz
D
D
Marsh
D J
DJ
Schramm
J
J
Wiestler
O D
OD
Parsons
R
R
Eng
C
C
von Deimling
A
A
D002879:Chromosomes, Human, Pair 10 / Q000235:genetics; D016147:Genes, Tumor Suppressor; D005819:Genetic Markers / Q000235:genetics; D018095:Germ-Line Mutation; D006801:Humans; D019656:Loss of Heterozygosity / Q000235:genetics; D008579:Meningioma / Q000235:genetics*; D051059:PTEN Phosphohydrolase; D010744:Phosphoric Monoester Hydrolases; D011110:Polymorphism, Genetic; D018807:Polymorphism, Single-Stranded Conformational; D017027:Protein Tyrosine Phosphatases / Q000235:genetics*; D017384:Sequence Deletion; D025521:Tumor Suppressor Proteins
D005819:Genetic Markers; D025521:Tumor Suppressor Proteins; D010744:Phosphoric Monoester Hydrolases; D017027:Protein Tyrosine Phosphatases; D051059:PTEN Phosphohydrolase; C494929:PTEN protein, human