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

Antoine M. Snijders, Brian L. Schmidt, Jane Fridlyand, Nusi Dekker, Daniel Pinkel, Richard C.K. Jordan, Donna G. Albertson

Research output: Contribution to journalArticle

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 <3Mb. 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.

Original languageEnglish (US)
Pages (from-to)4232-4242
Number of pages11
JournalOncogene
Volume24
Issue number26
DOIs
StatePublished - Jun 16 2005

Keywords

  • Amplicon
  • Array CGH
  • Hedgehog
  • Notch
  • Oral SCC

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics
  • Cancer Research

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