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.

Gene Expression Profiling of ErbB Receptors and Ligands in Human Meningiomas

“…The more benign tumors as meningiomas have not been characterized well up to now. Mutations in the NF2 gene and loss of chromosome 22q are the most common alterations found in sporadic meningiomas (3,4). Several extensive studies of molecular alterations were performed by genomic and cDNA microarray assays (5,6).…”

Mutational analysis of the NF2 gene in sporadic meningiomas by denaturing high-performance liquid chromatography

“…Denaturing high-performance liquid chromatography (DHPLC), based on the detection of heteroduplexes in PCR products by ion pair reverse-phase HPLC under partially denaturing conditions, is a highly sensitive and specific technique for mutation detection (10). Though DHPLC was used as a prescreening technique for heteroduplex analysis so as to detect mutations, the accurate prevalence of NF2 mutations in sporadic meningiomas using DHPLC has been rarely reported (11).…”

Neurofibromatosis 2 [Bilateral acoustic neurofibromatosis, central neurofibromatosis, NF2, neurofibromatosis type II]

“…31,32 • Individuals older than 30 years, with a unilateral vestibular schwannoma, have a negligible risk of developing NF2. 32,56 The offspring of individuals with unilateral vestibular schwannoma and no known family history of schwannomas do not have an increased incidence of either NF2 or unilateral vestibular schwannoma. Somatic involvement of the NF2 gene in isolated vestibular schwannomas is almost universal 31,57 ; however, the possibility exists that mutations in other genes on Chromosome 22 predispose to schwannoma development.…”

“…Somatic involvement of the NF2 gene in isolated vestibular schwannomas is almost universal 31,57 ; however, the possibility exists that mutations in other genes on Chromosome 22 predispose to schwannoma development. Mutations in INI1 (SMARCB1) result in schwannomatosis 56 and there are likely to be further genes that cause schwannomatosis and that could modify NF2. 58 Schwannomatosis is defined as multiple schwannomas without the vestibular schwannomas that are diagnostic of NF2.…”