title: Loss of heterozygosity at 1p-19q induces a global change in oligodendroglial tumor gene expression.
abstract: Oligodendroglial tumors presenting loss of heterozygosity (LOH) at 1p and 19q have been shown to be sensitive to chemotherapy, thus making 1p-19q status testing a key aspect in oligodendroglioma diagnosis and prognosis. Twenty-nine tumor samples (19 oligodendrogliomas, 10 oligoastrocytomas) were analyzed in order to obtain a molecular profile identifying those bearing 1p-19q LOH. Other genomic anomalies usually present in gliomas, such as EGFR amplification, CDKN2A/ARF deletion, 10q LOH and TP53 mutation, were also studied. Tumors with 1p-19q LOH overexpressed genes related to neurogenesis. Genes linked to immune response, proliferation and inflammation were overexpressed in the group with intact 1p-19q; this group could in turn be further divided in two subgroups: one overexpressing genes involved in immune response and inflammation that did not show major genetic aberrations other than the TP53 mutation and EGFR trisomy in a few cases, and another overexpressing genes related to immune response and proliferation that had a predominance of samples carrying several anomalies and presenting worse outcomes. This molecular signature was validated by analyzing a set of ten tumor samples (three oligodendrogliomas, seven oligoastrocytomas); all ten samples were correctly assigned. LOH at 1p-19q results in haploinsufficiency and copy number reduction of several genes, including NOTCH 2; this phenomenon produces a global change in gene expression inducing a pro-neural status that results in restrictions to cell migration and proliferation. Tumors without LOH at 1p-19q exhibit the opposite characteristics, explaining their more aggressive behavior.
authors: Department of Physical Chemistry, Universitat de Valencia, Dr. Moliner sn., 46100, Burjassot, Valencia, Spain.
authors: Rubén
authors: R
authors: Ferrer-Luna
authors: Research Foundation, Hospital General Universitario de Valencia, Valencia, Spain.
authors: Manuel
authors: M
authors: Mata
authors: Department of Neuropathology, FLENI, Montañeses 2325 (C1428AQK), Buenos Aires, Argentina.
authors: Lina
authors: L
authors: Núñez
authors: Department of Neuroimaging, FLENI, Buenos Aires, Argentina.
authors: Jorge
authors: J
authors: Calvar
authors: Research Foundation, Hospital Clínico Universitario, Valencia, Spain.
authors: Francisco
authors: F
authors: Dasí
authors: Department of Neuropathology, FLENI, Montañeses 2325 (C1428AQK), Buenos Aires, Argentina.
authors: Eugenia
authors: E
authors: Arias
authors: Neurosurgery Service, Hospital de la Ribera-Alzira, Valencia, Spain.
authors: José
authors: J
authors: Piquer
authors: Department of Pathology, University of Valencia, Valencia, Spain.
authors: Miguel
authors: M
authors: Cerdá-Nicolás
authors: Department of Neuropathology, FLENI, Montañeses 2325 (C1428AQK), Buenos Aires, Argentina.
authors: Ana Lía
authors: AL
authors: Taratuto
authors: Department of Neuropathology, FLENI, Montañeses 2325 (C1428AQK), Buenos Aires, Argentina.
authors: Gustavo
authors: G
authors: Sevlever
authors: Department of Physical Chemistry, Universitat de Valencia, Dr. Moliner sn., 46100, Burjassot, Valencia, Spain. bernardo.celda@uv.es.|CIBER BBN, ISC-III, Valencia, Spain. bernardo.celda@uv.es.
authors: Bernardo
authors: B
authors: Celda
authors: Department of Neuropathology, FLENI, Montañeses 2325 (C1428AQK), Buenos Aires, Argentina. hmartinetto@fleni.org.ar.
authors: Horacio
authors: H
authors: Martinetto
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D001932:Brain Neoplasms / Q000235:genetics*; D002675:Child, Preschool; D002872:Chromosome Deletion; D002878:Chromosomes, Human, Pair 1; D002888:Chromosomes, Human, Pair 19; D016000:Cluster Analysis; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D019656:Loss of Heterozygosity; D008875:Middle Aged; D009837:Oligodendroglioma / Q000235:genetics*; D020133:Reverse Transcriptase Polymerase Chain Reaction