PURPOSE: The purpose of this research was to examine the DNA methylation profile of schwannomas. EXPERIMENTAL DESIGN: We examined the DNA methylation status of 12 tumor-related genes (NF2, RB1, p14(ARF), p16(INK4a), p73, TIMP-3, MGMT, DAPK, THBS1, caspase-8, TP53, and GSTP1) in 44 sporadic and/or NF2-associated schwannomas using methylation-specific PCR. RESULTS: The most frequently methylated genes were THBS1 (36%), p73 (27%), MGMT (20%), NF2 (18%), and TIMP-3 (18%). The RB1/p16INK4a gene pair displayed aberrant methylayed alleles in 15% of cases, whereas methylation was relatively rare in the other genes (<5%). Methylation was tumor specific because it was absent in two nonneoplastic nerve sheath samples and two nonneoplastic brain samples studied as controls. CONCLUSIONS: Our findings indicate that aberrant methylation seems to be a mechanism for NF2 gene inactivation, considered an early step in schwannoma tumorigenesis, and as well, aberrant hypermethylation of other tumor-related genes might represent secondary events that also contribute to the development of these tumors.
PURPOSE: The purpose of this research was to examine the DNA methylation profile of schwannomas. EXPERIMENTAL DESIGN: We examined the DNA methylation status of 12 tumor-related genes (NF2, RB1, p14(ARF), p16(INK4a), p73, TIMP-3, MGMT, DAPK, THBS1, caspase-8, TP53, and GSTP1) in 44 sporadic and/or NF2-associated schwannomas using methylation-specific PCR. RESULTS: The most frequently methylated genes were THBS1 (36%), p73 (27%), MGMT (20%), NF2 (18%), and TIMP-3 (18%). The RB1/p16INK4a gene pair displayed aberrant methylayed alleles in 15% of cases, whereas methylation was relatively rare in the other genes (<5%). Methylation was tumor specific because it was absent in two nonneoplastic nerve sheath samples and two nonneoplastic brain samples studied as controls. CONCLUSIONS: Our findings indicate that aberrant methylation seems to be a mechanism for NF2 gene inactivation, considered an early step in schwannoma tumorigenesis, and as well, aberrant hypermethylation of other tumor-related genes might represent secondary events that also contribute to the development of these tumors.
Authors: Miguel Torres-Martín; Victor Martinez-Glez; Carolina Peña-Granero; Luis Lassaletta; Alberto Isla; Jose M de Campos; Giovanny R Pinto; Rommel R Burbano; Bárbara Meléndez; Javier S Castresana; Juan A Rey Journal: Clin Transl Oncol Date: 2012-10-02 Impact factor: 3.405
Authors: Maurits de Vries; Inge Briaire-de Bruijn; Anne-Marie Cleton-Jansen; Martijn J A Malessy; Andel G L van der Mey; Pancras C W Hogendoorn Journal: Virchows Arch Date: 2012-12-08 Impact factor: 4.064
Authors: M Eva Alonso; M Josefa Bello; Pilar Gonzalez-Gomez; Dolores Arjona; Jose M de Campos; Manuel Gutierrez; Juan A Rey Journal: J Neurooncol Date: 2004 Mar-Apr Impact factor: 4.130
Authors: Luis Lassaletta; Miguel Torres-Martín; Jesús San-Román-Montero; Javier S Castresana; Javier Gavilán; Juan Antonio Rey Journal: Eur Arch Otorhinolaryngol Date: 2012-11-21 Impact factor: 2.503