Apr 13, 2005

Rare amplicons implicate frequent deregulation of cell fate specification pathways in oral squamous cell carcinoma

Oncogene
Antoine M SnijdersDonna G Albertson

Abstract

Genomes of solid tumors are characterized by gains and losses of regions, which may contribute to tumorigenesis by altering gene expression. Often the aberrations are extensive, encompassing whole chromosome arms, which makes identification of candidate genes in these regions difficult. Here, we focused on narrow regions of gene amplification to facilitate identification of genetic pathways important in oral squamous cell carcinoma (SCC) development. We used array comparative genomic hybridization (array CGH) to define minimum common amplified regions and then used expression analysis to identify candidate driver genes in amplicons that spanned <3 Mb. We found genes involved in integrin signaling (TLN1), survival (YAP1, BIRC2), and adhesion and migration (TLN1, LAMA3, MMP7), as well as members of the hedgehog (GLI2) and notch (JAG1, RBPSUH, FJX1) pathways to be amplified and overexpressed. Deregulation of these and other members of the hedgehog and notch pathways (HHIP, SMO, DLL1, NOTCH4) implicates deregulation of developmental and differentiation pathways, cell fate misspecification, in oral SCC development.

  • References41
  • Citations144

References

  • References41
  • Citations144

Citations

Mentioned in this Paper

Biochemical Pathway
Gene Expression Regulation, Neoplastic
GLI2 protein, human
Cell Fate
Gene Amplification
Genome
Notch
Candidate Disease Gene
Array-Based Comparative Genomic Hybridization
NOTCH4 gene

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