title: NF2 tumor suppressor gene: a comprehensive and efficient detection of somatic mutations by denaturing HPLC and microarray-CGH.
abstract: The NF2 tumor suppressor gene, located in chromosome 22q12, is involved in the development of multiple tumors of the nervous system, either associated with neurofibromatosis 2 or sporadic ones, mainly schwannomas and meningiomas. In order to evaluate the role of the NF2 gene in sporadic central nervous system (CNS) tumors, we analyzed NF2 mutations in 26 specimens: 14 meningiomas, 4 schwannomas, 4 metastases, and 4 other histopathological types of neoplasms. Denaturing high performance liquid chromatography (denaturing HPLC) and comparative genomic hybridization on a DNA microarray (microarray- CGH) were used as scanning methods for small mutations and gross rearrangements respectively. Small mutations were identified in six out of seventeen meningiomas and schwannomas, one mutation was novel. Large deletions were detected in six meningiomas. All mutations were predicted to result in truncated protein or in the absence of a large protein domain. No NF2 mutations were found in other histopathological types of CNS tumors. These results provide additional evidence that mutations in the NF2 gene play an important role in the development of sporadic meningiomas and schwannomas. Denaturing HPLC analysis of small mutations and microarray-CGH of large deletions are complementary, fast, and efficient methods for the detection of mutations in tumor tissues.
authors.affiliation: Genetica y Biologia Molecular, Facultad de Farmacia y Bioquimica y Hospital de Clinicas, Universitdad de Buenos Aires, Junin 956, 1113 Buenos Aires, Argentina. iszijan@arnet.com.ar
authors.forename: Irene
authors.initials: I
authors.lastname: Szijan
authors.forename: Daniel
authors.initials: D
authors.lastname: Rochefort
authors.forename: Carl
authors.initials: C
authors.lastname: Bruder
authors.forename: Ezequiel
authors.initials: E
authors.lastname: Surace
authors.forename: Gloria
authors.initials: G
authors.lastname: Machiavelli
authors.forename: Viviana
authors.initials: V
authors.lastname: Dalamon
authors.forename: Javier
authors.initials: J
authors.lastname: Cotignola
authors.forename: Veronica
authors.initials: V
authors.lastname: Ferreiro
authors.forename: Alvaro
authors.initials: A
authors.lastname: Campero
authors.forename: Armando
authors.initials: A
authors.lastname: Basso
authors.forename: Jan P
authors.initials: JP
authors.lastname: Dumanski
authors.forename: Guy A
authors.initials: GA
authors.lastname: Rouleau
mesh_terms: D001483:Base Sequence / Q000235:genetics; D001932:Brain Neoplasms / Q000235:genetics* / Q000378:metabolism; D002851:Chromatography, High Pressure Liquid; D003062:Codon / Q000235:genetics; D004252:DNA Mutational Analysis; D005091:Exons / Q000235:genetics; D017353:Gene Deletion; D016515:Genes, Neurofibromatosis 2 / Q000502:physiology*; D005820:Genetic Testing; D006801:Humans; D008579:Meningioma / Q000235:genetics / Q000378:metabolism; D009154:Mutation / Q000235:genetics*; D009442:Neurilemmoma / Q000235:genetics / Q000378:metabolism; D025581:Neurofibromin 2 / Q000172:deficiency* / Q000235:genetics*; D009693:Nucleic Acid Hybridization; D020411:Oligonucleotide Array Sequence Analysis
chemical_list: D003062:Codon; D025581:Neurofibromin 2