Keiko Taniguchi-Ponciano1, Eduardo Peña-Martínez1, Gloria Silva-Román1, Sandra Vela-Patiño1, Ana Laura Guzman-Ortiz2, Hector Quezada2, Erick Gomez-Apo3, Laura Chavez-Macias3,4, Sophia Mercado-Medrez1, Guadalupe Vargas-Ortega5, Ana Laura Espinosa-de-Los-Monteros5, Baldomero Gonzales-Virla5, Aldo Ferreira-Hermosillo1,5, Etual Espinosa-Cardenas5, Claudia Ramirez-Renteria1,5, Ernesto Sosa5, Blas Lopez-Felix6, Gerardo Guinto6, Daniel Marrero-Rodríguez7, Moises Mercado1. 1. Unidad de Investigación Medica en Enfermedades Endocrinas, Hospital de Especialidades, Centro Medico Nacional Siglo XXI, Instituto Mexicano del Seguro Social, Av. Cuauhtémoc 330, Col. Doctores, Mexico D.F. 06720, Mexico. 2. Laboratorio de Investigacion en Inmunologia y Proteomica, Hospital Infantil de Mexico "Federico Gomez", Mexico City 06720, Mexico. 3. Área de Neuropatología, Servicio de Anatomía Patológica, Hospital General de México "Dr. Eduardo Liceaga", Ciudad de México 06720, Mexico. 4. Facultad de Medicina, Universidad Nacional Autonoma de México, Mexico City 04510, Mexico. 5. Servicio de Endocrinologia, Hospital de Especialidades, Centro Medico Nacional Siglo XXI, Instituto Mexicano del Seguro Social, Ciudad de México 06720, Mexico. 6. Servicio de Neurocirugia, Hospital de Especialidades, Centro Medico Nacional Siglo XXI, Instituto Mexicano del Seguro Social, Ciudad de México 06720, Mexico. 7. Catedra CONACyT-Laboratorio de Endocrinologia Experimental, Unidad de Investigación Medica en Enfermedades Endocrinas, Hospital de Especialidades, Centro Medico Nacional Siglo XXI, Instituto Mexicano del Seguro Social, Av. Cuauhtémoc 330, Col. Doctores, Mexico D.F. 06720, Mexico.
Abstract
BACKGROUND: Pituitary adenomas (PA) are the second most common tumor in the central nervous system and have low counts of mutated genes. Splicing occurs in 95% of the coding RNA. There is scarce information about the spliceosome and mRNA-isoforms in PA, and therefore we carried out proteomic and transcriptomic analysis to identify spliceosome components and mRNA isoforms in PA. METHODS: Proteomic profile analysis was carried out by nano-HPLC and mass spectrometry with a quadrupole time-of-flight mass spectrometer. The mRNA isoforms and transcriptomic profiles were carried out by microarray technology. With proteins and mRNA information we carried out Gene Ontology and exon level analysis to identify splicing-related events. RESULTS: Approximately 2000 proteins were identified in pituitary tumors. Spliceosome proteins such as SRSF1, U2AF1 and RBM42 among others were found in PA. These results were validated at mRNA level, which showed up-regulation of spliceosome genes in PA. Spliceosome-related genes segregate and categorize PA tumor subtypes. The PA showed alterations in CDK18 and THY1 mRNA isoforms which could be tumor specific. CONCLUSIONS: Spliceosome components are significant constituents of the PA molecular machinery and could be used as molecular markers and therapeutic targets. Splicing-related genes and mRNA-isoforms profiles characterize tumor subtypes.
BACKGROUND:Pituitary adenomas (PA) are the second most common tumor in the central nervous system and have low counts of mutated genes. Splicing occurs in 95% of the coding RNA. There is scarce information about the spliceosome and mRNA-isoforms in PA, and therefore we carried out proteomic and transcriptomic analysis to identify spliceosome components and mRNA isoforms in PA. METHODS: Proteomic profile analysis was carried out by nano-HPLC and mass spectrometry with a quadrupole time-of-flight mass spectrometer. The mRNA isoforms and transcriptomic profiles were carried out by microarray technology. With proteins and mRNA information we carried out Gene Ontology and exon level analysis to identify splicing-related events. RESULTS: Approximately 2000 proteins were identified in pituitary tumors. Spliceosome proteins such as SRSF1, U2AF1 and RBM42 among others were found in PA. These results were validated at mRNA level, which showed up-regulation of spliceosome genes in PA. Spliceosome-related genes segregate and categorize PA tumor subtypes. The PA showed alterations in CDK18 and THY1 mRNA isoforms which could be tumor specific. CONCLUSIONS: Spliceosome components are significant constituents of the PA molecular machinery and could be used as molecular markers and therapeutic targets. Splicing-related genes and mRNA-isoforms profiles characterize tumor subtypes.
Entities:
Keywords:
alternative splicing; mRNA isoforms; molecular markers; pituitary adenomas
Authors: Paul J Newey; M Andrew Nesbit; Andrew J Rimmer; Rosie A Head; Caroline M Gorvin; Moustafa Attar; Lorna Gregory; John A H Wass; David Buck; Niki Karavitaki; Ashley B Grossman; Gilean McVean; Olaf Ansorge; Rajesh V Thakker Journal: J Clin Endocrinol Metab Date: 2013-02-28 Impact factor: 5.958