Prognostic stratification of adult primary glioblastoma multiforme patients based on their tumor gene amplification profiles
| Autor: | Maria do Carmo Lopes, Hermínio Tão, Ana Filipa Guedes, Maria C. Patino-Alonso, Pablo Sousa, María Dolores Tabernero, Olinda Rebelo, María González-Tablas, Ana Luísa Vital, Ana Belen Nieto, Álvaro Otero, Pim J. French, Maria Rosário Almeida, Alberto Orfao, Luis A. Corchete, Marcos Barbosa, Inês Crespo |
|---|---|
| Přispěvatelé: | Red Temática de Investigación Cooperativa en Cáncer (España), Instituto de Salud Carlos III, Ministerio de Economía y Competitividad (España), European Commission, Junta de Castilla y León, Neurology |
| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
Gene amplification Subtypes Survival genes supresores de tumores glioblastoma Chromosome Biology Classification DNA sequencing Prognostic stratification 03 medical and health sciences 3201.01 Oncología 030104 developmental biology Oncology Primary Glioblastoma Multiforme síntomas de cáncer Chromosomal region Gene duplication Cancer research EGFR Gene Amplification Genes Tumor Suppressor Gene 3205.07 Neurología Research Paper |
| Zdroj: | GREDOS: Repositorio Institucional de la Universidad de Salamanca Universidad de Salamanca (USAL) Digital.CSIC: Repositorio Institucional del CSIC Consejo Superior de Investigaciones Científicas (CSIC) GREDOS. Repositorio Institucional de la Universidad de Salamanca instname Digital.CSIC. Repositorio Institucional del CSIC Oncotarget Oncotarget, 9(46), 28083-28102. Impact Journals LLC |
| ISSN: | 1949-2553 |
| DOI: | 10.18632/oncotarget.25562 |
| Popis: | Several classification systems have been proposed to address genomic heterogeneity of glioblastoma multiforme, but they either showed limited prognostic value and/or are difficult to implement in routine diagnostics. Here we propose a prognostic stratification model for these primary tumors based on tumor gene amplification profiles, that might be easily implemented in routine diagnostics, and potentially improve the patients management. Gene amplification profiles were prospectively evaluated in 80 primary glioblastoma multiforme tumors using single-nucleotide polymorphism arrays and the results obtained validated in publicly available data from 267/347 cases. Gene amplification was detected in 45% of patients, and chromosome 7p11.2 including the EGFR gene, was the most frequently amplified chromosomal region – either alone (18%) or in combination with amplification of DNA sequences in other chromosomal regions (10% of cases). Other frequently amplified DNA sequences included regions in chromosomes 12q(10%), 4q12(7%) and 1q32.1(4%). Based on their gene amplification profiles, glioblastomas were subdivided into: i) tumors with no gene amplification (55%); ii) tumors with chromosome 7p/EGFR gene amplification (with or without amplification of other chromosomal regions) (38%); and iii) glioblastoma multiforme with a single (11%) or multiple (6%) amplified DNA sequences in chromosomal regions other than chromosome 7p. From the prognostic point of view, these amplification profiles showed a significant impact on overall survival of glioblastoma multiforme patients (p>0.001). Based on these gene amplification profiles, a risk-stratification scoring system was built for prognostic stratification of glioblastoma which might be easily implemented in routine diagnostics, and potentially contribute to improved patient management. This work was supported by RETICC RD06/0020/0035, RD06/0020/0059 and RD12/0036/0048 grants from Red Temática de Investigación Cooperativa en Cáncer (RTICC), Instituto de Salud Carlos III, Ministerio de Economía y Competitividad, (Madrid, Spain and FONDOS FEDER), AES PI16/000476 (Instituto de Salud Carlos III, Madrid, Spain and FONDOS FEDER), GRS909A14 (JCYL) and CB16/12/00400 grant (CIBERONC, Instituto de Salud Carlos III, Ministerio de Economía y Competitividad, Madrid, Spain and FONDOS FEDER). |
| Databáze: | OpenAIRE |
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