A global view of the oncogenic landscape in nasopharyngeal carcinoma: an integrated analysis at the genetic and expression levels

Autor: Sim K. Sihota, Lawrence S. Young, Wenbin Wei, Xiaoyi Chen, Andrew I. Bell, Yunhong Yao, Christopher W. Dawson, K. Dalia Derkaoui, John R. Arrand, Aicha Amari, Stephanie L. Maloney, Jian Yong Shao, Chunfang Hu, Paul Murray, Ciaran B J Woodman, Irène Joab, John M. Nicholls
Rok vydání: 2012
Předmět:
Herpesvirus 4
Human
Transcription
Genetic
lcsh:Medicine
Gene Expression
Molecular cell biology
DNA amplification
Gene duplication
Gene expression
Basic Cancer Research
lcsh:Science
Promoter Regions
Genetic
Oligonucleotide Array Sequence Analysis
Genetics
Regulation of gene expression
Multidisciplinary
Cancer Risk Factors
Homozygote
Genomics
Head and Neck Tumors
Up-Regulation
Gene Expression Regulation
Neoplastic
Nucleic acids
Oncology
Medicine
Female
Research Article
Gene Expression Regulation
Viral
Genetic Causes of Cancer
Nasopharyngeal neoplasm
Biology
RC0254
Viral Matrix Proteins
Viral Proteins
Head and Neck Squamous Cell Carcinoma
medicine
Humans
Gene
Gene Expression Profiling
lcsh:R
Carcinoma
Chromosome
Cancers and Neoplasms
Nasopharyngeal Neoplasms
DNA
medicine.disease
Gene expression profiling
Nasopharyngeal carcinoma
Cancer research
lcsh:Q
Genome Expression Analysis
Gene Deletion
Zdroj: PLoS ONE
PLoS ONE, Vol 7, Iss 7, p e41055 (2012)
ISSN: 1932-6203
Popis: 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.
Databáze: OpenAIRE
Externí odkaz: