Inactivation patterns of NF2 and DAL-1/4.1B (EPB41L3) in sporadic meningioma.
The molecular basis of tumorigenesis and tumor progression in meningiomas is not fully understood. The neurofibromatosis 2 (NF2) locus is inactivated in 50-60% of sporadic meningiomas, but the genetic basis of sporadic meningiomas not inactivated at the NF2 locus remains unclear. Specifically, there is conflicting data regarding the role of the tumor suppressor gene DAL-1/4.1B. Using microsatellite markers, we studied 63 sporadic meningiomas to determine loss of heterozygosity (LOH) at the NF2 and DAL-1/4.1B loci. Array comparative genomic hybridization analysis of 52 of these tumors was performed to determine copy number changes on chromosomes 18 and 22. Forty-one of 62 informative tumors showed LOH at the NF2 locus (66%) while only 12 of 62 informative tumors (19%) showed LOH of DAL-1/4.1B. Eleven of 12 (92%) tumors with DAL-1/4.1B LOH also had NF2 LOH. Monosomy or large deletions of chromosomes 18 and 22 were the main mechanism for LOH in these tumors. These studies implicate the DAL-1/4.1B locus in sporadic meningiomas less commonly than reported previously, and suggest that it is a progression rather than an initiation locus. Furthermore, we found the majority of meningiomas developed monosomy rather than isodisomy at the NF2 and DAL-1/4.1B loci as the mechanism for LOH.
Nunes
Fabio
F
Department of Neurology, Massachusetts General Hospital, Building 149, 13th Street, Charlestown, MA 02129, USA. fnunes@partners.org
Shen
Yiping
Y
Niida
Yo
Y
Beauchamp
Roberta
R
Stemmer-Rachamimov
Anat O
AO
Ramesh
Vijaya
V
Gusella
James
J
MacCollin
Mia
M
D002887:Chromosomes, Human, Pair 18; D002892:Chromosomes, Human, Pair 22; D016515:Genes, Neurofibromatosis 2; D016147:Genes, Tumor Suppressor; D006801:Humans; D019656:Loss of Heterozygosity; D008565:Membrane Proteins / Q000235:genetics*; D008577:Meningeal Neoplasms / Q000235:genetics*; D008579:Meningioma / Q000235:genetics*; D008840:Microfilament Proteins; D018895:Microsatellite Repeats; D025521:Tumor Suppressor Proteins / Q000235:genetics*
C116887:EPB41L3 protein, human; D008565:Membrane Proteins; D008840:Microfilament Proteins; D025521:Tumor Suppressor Proteins