GADD45A and EPB41 as tumor suppressor genes in meningioma pathogenesis.
Piaskowski
S, Rieske
P, Szybka
M, Wozniak K, Bednarek
A, Pluciennik
E, Jaskolski
D, Sikorska
B, Liberski
PP.
Department of Molecular Pathology and Neuropathology, Chair of Oncology,
Medical University, Czechoslowacka st. 8/10, 92-216 Lodz, Poland.
Deletions of 1p occur in approximately 30% of meningiomas.
Based on loss of heterozygosity (LOH) analysis, two
regions on 1p have been suspected to be carriers of tumor suppressor genes. We
chose the GADD45A and EPB41 genes as tumor suppressor candidates based on their
function and chromosomal localization. We analyzed 19 cases of meningioma with LOH of 1p by means of sequencing of the
GADD45A gene and Western blotting of the GADD45a protein. Twenty cases of meningioma without 1p LOH were also analyzed by Western
blotting to find out if changes of the GADD45a protein expression occurred.
Nineteen samples with 1p LOH (12 grade I; 7 grade II,
WHO classification) and 20 samples without 1p LOH (18 grade I; 2 grade II) were
also analyzed by means of real-time polymerase chain reaction to find
abnormalities in EPB41 mRNA levels in meningioma. LOH
analysis was performed using seven microsatellite
markers: D1S508 (1p36.2), D1S199 (1p36.1) D1S2734 (1p36.1), D1S2720 (1p34),
D1S197 (1p32), D1S162 (1p32), D1S429 (1p11). LOH analysis confirmed previously
described localization of putative tumor suppressor genes on 1p and involvement
in meningioma pathogenesis (1p36 and 1p32). The open
reading frame of GADD45A and intron splicing sites
showed neither mutations nor polymorphisms. GADD45a protein molecular weight
and expression level were unaltered in meningiomas
with and without 1p LOH. We conclude that the GADD45A gene is not involved in meningioma tumorigenesis. EPB41
gene expression was unchanged in all analyzed meningiomas.
This suggests that involvement of the EPB41 gene (4.1R protein) in meningioma pathogenesis should be reconsidered.
PMID: 16157202 [PubMed - in process]