Genomic deletions at 1p and 14q are associated with an abnormal cDNA microarray gene expression pattern in meningiomas but not in schwannomas.
The molecular pathology of meningiomas and shwannomas involve the inactivation of the NF2 gene to generate grade I tumors. Genomic losses at 1p and 14q are observed in both neoplasms, although more frequently in meningiomas. The inactivation of unidentified genes located in these regions appears associated with tumor progression in meningiomas, but no clues to its molecular/clinical meaning are available in schwannomas. Recent microarray gene expression studies have demonstrated the existence of molecular subgroups in both entities. In the present study, we correlated the presence of genomic deletions at 1p, 14q, and 22q with the expression patterns of 96 tumor-related genes obtained by cDNA low-density microarrays in a series of 65 tumors including 42 meningiomas and 23 schwannomas. Two expression pattern groups were identified by cDNA mycroarray analysis when compared to the expression pattern in normal control RNA in both meningiomas and schwannomas, each one with patterns similar and different from the normal control. Meningioma and schwannoma subgroups differed in the expression of 38 and 16 genes, respectively. Using MLPA and microsatellites, we identified genomic losses at 1p, 14q, and 22q at nonrandom frequencies (12.5-69%) in meningiomas and schwannomas. Losses at 22q were almost equally frequent in both molecular expression subgroups in both neoplasms. However, deletions at 1p and 14q accumulated in meningiomas with a gene expression pattern different from the normal pattern, whereas the inverse situation occurred in schwannomas. Those anomalies characterized the schwannomas with expression pattern similar to the normal control. These findings suggest that deletions at 1p and 14q enhance the development of an abnormal tumor-related gene expression pattern in meningiomas, but this fact is not corroborated in schwannomas.
Martínez-Glez
Victor
V
Research Unit-Unidad de Investigación, Hospital Universiatrio La Paz, Paseo Castellana 261, 28046 Madrid, Spain.
Alvarez
Luis
L
Franco-Hernández
Carmen
C
Torres-Martin
Miguel
M
de Campos
Jose M
JM
Isla
Alberto
A
Vaquero
Jesús
J
Lassaletta
Luis
L
Castresana
Javier S
JS
Casartelli
Cacilda
C
Rey
Juan A
JA
D002872:Chromosome Deletion; D002878:Chromosomes, Human, Pair 1; D002883:Chromosomes, Human, Pair 14; D018076:DNA, Complementary / Q000235:genetics; D020869:Gene Expression Profiling; D023281:Genomics; D006801:Humans; D008579:Meningioma / Q000235:genetics*; D009442:Neurilemmoma / Q000235:genetics*; D020411:Oligonucleotide Array Sequence Analysis
D018076:DNA, Complementary