Genome-wide profiling of oral squamous cell carcinoma

J Pathol. 2004 Nov;204(3):326-32. doi: 10.1002/path.1640.

Abstract

Oral squamous cell carcinoma (OSCC) is a common malignancy, the incidence of which is particularly high in some Asian countries due to the geographically linked areca quid (AQ) chewing habit. In this study, array-based comparative genomic hybridization was used to screen microdissected OSCCs for genome-wide alterations. The highest frequencies of gene gain were detected for TP63, Serpine1, FGF4/FGF3, c-Myc and DMD. The highest frequencies of deletion were detected for Caspase8 and MTAP. Gained genes, classified by hierarchical clustering, were mainly on 17q21-tel; 20q; 11q13; 3q27-29 and the X chromosome. Among these, gains of EGFR at 7p, FGF4/FGF3, CCND1 and EMS1 at 11q13, and AIB1 at 20q were significantly associated with lymph node metastasis. The genomic profiles of FHIT and EXT1 in AQ-associated and non-AQ-associated OSCCs exhibited the most prominent differences. RT-PCR confirmed the significant increase of TP63 and Serpine1 mRNA expression in OSCC relative to non-malignant matched tissue. A significant increase in Serpine1 immunoreactivity was observed from non-malignant matched tissue to OSCC. However, there was no correlation between the frequent genomic loss of Caspase 8 and a significant decrease in Caspase8 expression. These data demonstrate that genomic profiling can be useful in analysing pathogenetic events involved in the genesis or progression of OSCC.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Carcinoma, Squamous Cell / genetics*
  • Caspase 8
  • Caspases / analysis
  • Cluster Analysis
  • DNA, Neoplasm / genetics*
  • Fibroblast Growth Factor 3
  • Fibroblast Growth Factor 4
  • Fibroblast Growth Factors / analysis
  • Genes, myc / genetics
  • Humans
  • Immunohistochemistry / methods
  • Lymphatic Metastasis / genetics
  • Middle Aged
  • Mouth Neoplasms / genetics*
  • Neoplasm Proteins / genetics*
  • Nucleic Acid Hybridization / methods
  • Oligonucleotide Array Sequence Analysis / methods
  • Plasminogen Activator Inhibitor 1 / analysis
  • Proto-Oncogene Proteins / analysis
  • RNA, Messenger / analysis
  • RNA, Neoplasm / analysis
  • Reverse Transcriptase Polymerase Chain Reaction / methods

Substances

  • DNA, Neoplasm
  • FGF3 protein, human
  • FGF4 protein, human
  • Fibroblast Growth Factor 3
  • Fibroblast Growth Factor 4
  • Neoplasm Proteins
  • Plasminogen Activator Inhibitor 1
  • Proto-Oncogene Proteins
  • RNA, Messenger
  • RNA, Neoplasm
  • Fibroblast Growth Factors
  • CASP8 protein, human
  • Caspase 8
  • Caspases