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Frequency of NFKBIA deletions is low in glioblastomas and skewed in glioblastoma neurospheres.
Patanè, Monica; Porrati, Paola; Bottega, Elisa; Morosini, Sara; Cantini, Gabriele; Girgenti, Vita; Rizzo, Ambra; Eoli, Marica; Pollo, Bianca; Sciacca, Francesca L; Pellegatta, Serena; Finocchiaro, Gaetano.
Afiliação
  • Finocchiaro G; Molecular Neuro-Oncology Unit, IRCCS Foundation "C,Besta" Neurological Institute, via Celoria 11, 20133 Milan, Italy. gaetano.finocchiaro@gmail.com.
Mol Cancer ; 12: 160, 2013 Dec 11.
Article em En | MEDLINE | ID: mdl-24330732
ABSTRACT
The NF-kB family of transcription factors is up-regulated in inflammation and different cancers. Recent data described heterozygous deletions of the NF-kB Inhibitor alpha gene (NFKBIA) in about 20% of glioblastomas (GBM) deletions were mutually exclusive with epidermal growth factor receptor (EGFR) amplification, a frequent event in GBM. We assessed the status of NFKBIA and EGFR in 69 primary GBMs and in corresponding neurospheres (NS). NFKBIA deletion was investigated by the copy number variation assay (CNV); EGFR amplification by CNV ratio with HGF; expression of EGFR and EGFRvIII by quantitative PCR or ReverseTranscriptase PCR. Heterozygous deletions of NFKBIA were present in 3 of 69 primary GBMs and, surprisingly, in 30 of 69 NS. EGFR amplification was detected in 36 GBMs in corresponding NS, amplification was lost in 13 cases and reduced in 23 (10 vs 47 folds in NS vs primary tumors; p < 0.001). The CNV assay was validated investigating HPRT1 on chromosome X in females and males. Results of array-CGH performed on 3 primary GBMs and 1 NS line were compatible with the CNV assay. NS cells with NFKBIA deletion had increased nuclear activity of p65 (RelA) and increased expression of the NF-kB target IL-6. In absence of EGF in the medium, EGFR amplification was more conserved and NFKBIA deletion less frequent point to a low frequency of NFKBIA deletions in GBM and suggest that EGF in the culture medium of NS may affect frequency not only of EGFR amplifications but also of NFKBIA deletions.
Assuntos

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Neoplasias Encefálicas / Glioblastoma / Proteínas I-kappa B / Receptores ErbB Limite: Adolescent / Adult / Aged / Female / Humans / Male / Middle aged Idioma: En Revista: Mol Cancer Assunto da revista: NEOPLASIAS Ano de publicação: 2013 Tipo de documento: Article

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Neoplasias Encefálicas / Glioblastoma / Proteínas I-kappa B / Receptores ErbB Limite: Adolescent / Adult / Aged / Female / Humans / Male / Middle aged Idioma: En Revista: Mol Cancer Assunto da revista: NEOPLASIAS Ano de publicação: 2013 Tipo de documento: Article