title: Alteration of major vault protein in human glioblastoma and its relation with EGFR and PTEN status.
abstract: Glioblastoma (GBM) is the most frequent and malignant primary brain tumor. Conventional therapy of surgical removal, radiation and chemotherapy is largely palliative. Major vault protein (MVP), the main component of the vault organelle has been associated with multidrug resistance by reducing cellular accumulation of chemotherapeutic agents. With regard to cancer, MVP has been shown to be overexpressed in drug resistance development and malignant progression. The aim of the present study was to evaluate the MVP gene dosage levels in 113 archival samples from GBM and its correlation with patients' survival and epidermal growth factor receptor (EGFR) and phosphatase and tensin homolog (PTEN) gene dosages. Fluorescent in situ hybridization revealed polysomy of chromosome 7 in 76.1% of the GBMs and EGFR amplification in a 64.6% of the tumors. Genetic status of EGFR, PTEN and MVP copies was determined by multiplex ligation-dependent probe amplification (MLPA) technique. 31% of the tumors showed the EGFR is variant III mutation (EGFRvIII) mutation and 74.3% of them presented amplification of MVP gene. Amplification of EGFR and MVP was found in a 63.7% and 56.6% of the GBM, respectively. An inverse correlation between MVP and PTEN dosage values was observed. Besides, an inverse relationship between the survival of the patients treated with chemotherapy and the levels of MVP copies was determined. In conclusion, our study reveals an important role of MVP, together with EGFRvIII and PTEN, in the progression of GBM and proposes it as a novel and interesting target for new treatment approaches.
authors: Department of Pathology, Universitat de València, Valencia, Spain.
authors: L
authors: L
authors: Navarro
authors: Department of Pathology, Universitat de València, Valencia, Spain. Electronic address: rosario.gil-benso@uv.es.
authors: R
authors: R
authors: Gil-Benso
authors: Department of Pathology, Universitat de València, Valencia, Spain.
authors: J
authors: J
authors: Megías
authors: Department of Pathology, Universitat de València, Valencia, Spain.
authors: L
authors: L
authors: Muñoz-Hidalgo
authors: Department of Pathology, Universitat de València, Valencia, Spain.
authors: T
authors: T
authors: San-Miguel
authors: Department of Pathology, Universitat de València, Valencia, Spain.
authors: R C
authors: RC
authors: Callaghan
authors: Department of Neurosurgery, Clinic Hospital, Valencia, Spain.
authors: J M
authors: JM
authors: González-Darder
authors: Department of Pathology, Universitat de València, Valencia, Spain.
authors: C
authors: C
authors: López-Ginés
authors: Department of Pathology, Universitat de València, Valencia, Spain; Service of Pathology, Clinic Hospital, Valencia, Spain.
authors: M J
authors: MJ
authors: Cerdá-Nicolás
mesh_terms: D000328:Adult; D000368:Aged; D001932:Brain Neoplasms / Q000235:genetics / Q000378:metabolism*; D002897:Chromosomes, Human, Pair 7 / Q000235:genetics; D066246:ErbB Receptors / Q000235:genetics / Q000378:metabolism*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics*; D005909:Glioblastoma / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation / Q000235:genetics; D051059:PTEN Phosphohydrolase / Q000235:genetics / Q000378:metabolism*; D018709:Statistics, Nonparametric; D020394:Vault Ribonucleoprotein Particles / Q000378:metabolism*; D055815:Young Adult; D000099187:Major Vault Protein
chemical_list: D066246:ErbB Receptors; D051059:PTEN Phosphohydrolase; D020394:Vault Ribonucleoprotein Particles; D000099187:Major Vault Protein; C494929:PTEN protein, human
keywords: epidermal growth factor receptor variant III (EGFRvIII); epidermal growth factor receptor wild type (EGFRwt); glioblastoma (GBM); major vault protein (MVP); multiplex ligation-dependent probe amplification (MLPA); phosphatase and tensin homolog (PTEN)