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

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.

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Acknowledgements

We thank members of the UCSF Comprehensive Cancer Center Genome Analysis Shared Resource Facility, Sonia Mirza, Julie Weng and Maimie Yu, and Facility Manager, David Ginzinger for carrying out the quantitative RT–PCR and TP53 sequencing. This work was supported by NIH grants CA90421, CA94407, CA95231 and DE13904, and Tobacco-Related Disease Research Program grant 11RT-0141. BLS is an appointee of the Western Oral Research Consortium (NIH K12 DE14609).

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Correspondence to Donna G Albertson.

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Supplementary Information accompanies the paper on Oncogene website (http://www.nature.com/onc)

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Snijders, A., Schmidt, B., Fridlyand, J. et al. Rare amplicons implicate frequent deregulation of cell fate specification pathways in oral squamous cell carcinoma. Oncogene 24, 4232–4242 (2005). https://doi.org/10.1038/sj.onc.1208601

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