title: A global view of the oncogenic landscape in nasopharyngeal carcinoma: an integrated analysis at the genetic and expression levels.
abstract: Previous studies have reported that the tumour cells of nasopharyngeal carcinoma (NPC) exhibit recurrent chromosome abnormalities. These genetic changes are broadly assumed to lead to changes in gene expression which are important for the pathogenesis of this tumour. However, this assumption has yet to be formally tested at a global level. Therefore a genome wide analysis of chromosome copy number and gene expression was performed in tumour cells micro-dissected from the same NPC biopsies. Cellular tumour suppressor and tumour-promoting genes (TSG, TPG) and Epstein-Barr Virus (EBV)-encoded oncogenes were examined. The EBV-encoded genome maintenance protein EBNA1, along with the putative oncogenes LMP1, LMP2 and BARF1 were expressed in the majority of NPCs that were analysed. Significant downregulation of expression in an average of 76 cellular TSGs per tumour was found, whilst a per-tumour average of 88 significantly upregulated, TPGs occurred. The expression of around 60% of putative TPGs and TSGs was both up-and down-regulated in different types of cancer, suggesting that the simplistic classification of genes as TSGs or TPGs may not be entirely appropriate and that the concept of context-dependent onco-suppressors may be more extensive than previously recognised. No significant enrichment of TPGs within regions of frequent genomic gain was seen but TSGs were significantly enriched within regions of frequent genomic loss. It is suggested that loss of the FHIT gene may be a driver of NPC tumourigenesis. Notwithstanding the association of TSGs with regions of genomic loss, on a gene by gene basis and excepting homozygous deletions and high-level amplification, there is very little correlation between chromosomal copy number aberrations and expression levels of TSGs and TPGs in NPC.
authors: School of Cancer Sciences, University of Birmingham, Birmingham, United Kingdom.
authors: Chunfang
authors: C
authors: Hu
authors: Wenbin
authors: W
authors: Wei
authors: Xiaoyi
authors: X
authors: Chen
authors: Ciaran B
authors: CB
authors: Woodman
authors: Yunhong
authors: Y
authors: Yao
authors: John M
authors: JM
authors: Nicholls
authors: Irène
authors: I
authors: Joab
authors: Sim K
authors: SK
authors: Sihota
authors: Jian-Yong
authors: JY
authors: Shao
authors: K Dalia
authors: KD
authors: Derkaoui
authors: Aicha
authors: A
authors: Amari
authors: Stephanie L
authors: SL
authors: Maloney
authors: Andrew I
authors: AI
authors: Bell
authors: Paul G
authors: PG
authors: Murray
authors: Christopher W
authors: CW
authors: Dawson
authors: Lawrence S
authors: LS
authors: Young
authors: John R
authors: JR
authors: Arrand
mesh_terms: D002277:Carcinoma / Q000378:metabolism* / Q000821:virology*; D005260:Female; D017353:Gene Deletion; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D015967:Gene Expression Regulation, Viral; D004854:Herpesvirus 4, Human / Q000378:metabolism; D006720:Homozygote; D006801:Humans; D009303:Nasopharyngeal Neoplasms / Q000378:metabolism* / Q000821:virology*; D020411:Oligonucleotide Array Sequence Analysis; D011401:Promoter Regions, Genetic; D014158:Transcription, Genetic; D015854:Up-Regulation; D014763:Viral Matrix Proteins / Q000096:biosynthesis; D014764:Viral Proteins / Q000096:biosynthesis
chemical_list: C086495:BARF1 protein, Human herpesvirus 4; C037662:EBV-associated membrane antigen, Epstein-Barr virus; D014763:Viral Matrix Proteins; D014764:Viral Proteins