Frequency of NFKBIA deletions is low in glioblastomas and skewed in glioblastoma neurospheres

Molecular Cancer

Research

Gabriele Cantini¹  Sara Morosini¹  Paola Porrati²  Elisa Bottega²  Marica Eoli²  Monica Patanè²  Gaetano Finocchiaro³  Serena Pellegatta³  Bianca Pollo⁴  Ambra Rizzo⁵  Francesca L Sciacca⁵  Vita Girgenti⁵ 

[1] Department of Experimental Oncology, IFOM-IEO Campus, via Adamello 16, 20139, Milan, Italy;Molecular Neuro-Oncology Unit, IRCCS Foundation “C.Besta” Neurological Institute, via Celoria 11, 20133, Milan, Italy;Molecular Neuro-Oncology Unit, IRCCS Foundation “C.Besta” Neurological Institute, via Celoria 11, 20133, Milan, Italy;Department of Experimental Oncology, IFOM-IEO Campus, via Adamello 16, 20139, Milan, Italy;Neuropathology Unit, IRCCS Foundation “C.Besta” Neurological Institute, via Celoria 11, 20133, Milan, Italy;Unit of Clinical Pathology and Medical Genetics, IRCCS Foundation “C.Besta” Neurological Institute, via Celoria 11, 20133, Milan, Italy;

关键词: Epidermal Growth Factor Receptor;    Copy Number Variation;    Epidermal Growth Factor Receptor Expression;    Epidermal Growth Factor Receptor Gene;    Heterozygous Deletion;   

DOI  :  10.1186/1476-4598-12-160

 received in 2013-08-14, accepted in 2013-11-28,  发布年份 2013

来源: Springer

【 摘 要 】

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.

【 授权许可】

Unknown   
© Patanè et al.; licensee BioMed Central Ltd. 2013. This article is published under license to BioMed Central Ltd. This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.