Genome-wide analysis of oral squamous cell carcinomas revealed over expression of ISG15, Nestin and WNT11

Oral Dis. 2012 Jul;18(5):469-76. doi: 10.1111/j.1601-0825.2011.01894.x. Epub 2012 Jan 18.

Abstract

Background: Multistep pathways and mechanisms are involved in the development of oral cancer. Chromosomal alterations are one of such key mechanisms implicated oral carcinogenesis. Therefore, this study aims to determine the genomic copy number alterations (CNAs) in oral squamous cell carcinoma (OSCC) using array comparative genomic hybridization (aCGH) and in addition attempt to correlate CNAs with modified gene expression.

Materials and methods: Genome-wide screening was performed on 15 OSCCs using high-density aCGH. On the basis of pathway analysis, three genes (ISG15, Nestin and WNT11) which mapped to CNA regions were selected for further evaluation of their mRNA expression using quantitative reverse transcriptase PCR (qRT-PCR).

Results: Copy number alterations were observed on multiple genomic regions, including amplifications on 1p, 3q, 5p, 6p, 7p, 8q, 9q, 11q, 12q, 16p, 18p and deletions on 3p, 7q, 8p, 11q, 19q and 20q. Among the three selected genes, ISG15 had the highest mRNA expression level with a 22.5-fold increase, followed by Nestin with a 4.5-fold increase and WNT11 with a 2.5-fold increase.

Conclusions: This study has identified several major CNAs in oral cancer genomes and indicated that this correlates with over expression of the ISG15, WNT11, and Nestin genes.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Carcinoma, Squamous Cell / genetics*
  • Carcinoma, Squamous Cell / metabolism
  • Comparative Genomic Hybridization
  • Cytokines / biosynthesis
  • Cytokines / genetics*
  • DNA Copy Number Variations
  • Female
  • Gene Expression Profiling
  • Gene Expression Regulation, Neoplastic
  • Genome-Wide Association Study
  • Humans
  • Intermediate Filament Proteins / biosynthesis
  • Intermediate Filament Proteins / genetics*
  • Male
  • Middle Aged
  • Mouth Neoplasms / genetics*
  • Mouth Neoplasms / metabolism
  • Nerve Tissue Proteins / biosynthesis
  • Nerve Tissue Proteins / genetics*
  • Nestin
  • Reverse Transcriptase Polymerase Chain Reaction
  • Signal Transduction / genetics
  • Ubiquitins / biosynthesis
  • Ubiquitins / genetics*
  • Wnt Proteins / biosynthesis
  • Wnt Proteins / genetics*

Substances

  • Cytokines
  • Intermediate Filament Proteins
  • NES protein, human
  • Nerve Tissue Proteins
  • Nestin
  • Ubiquitins
  • Wnt Proteins
  • Wnt11 protein, human
  • ISG15 protein, human