Research article summary (published 30 Oct 2009):

Multiple pathways in the FGF signaling network are frequently deregulated by gene amplification in oral dysplasias.

Full Abstract

Genetic alteration in oral premalignant lesions (OPLs), the precursors of oral squamous cell carcinomas (OSCCs), may represent key changes in disease initiation and development. We ask if DNA amplification occurs at this early stage of cancer development and which oncogenic pathways are disrupted in OPLs. Here, we evaluated 50 high-grade dysplasias and low-grade dysplasias that later progressed to cancer for gene dosage aberrations using tiling-path DNA microarrays. Early occurrences of DNA amplification and homozygous deletion were frequently detected, with 40% (20/50) of these early lesions exhibiting such features. Expression for 88 genes in 7 recurrent amplicons were evaluated in 5 independent head and neck cancer datasets, with 40 candidates found to be overexpressed relative to normal tissues. These genes were significantly enriched in the canonical ERK/MAPK, FGF, p53, PTEN and PI3K/AKT signaling pathways (p = 8.95 x 10(-3) to 3.18 x 10(-2)). These identified pathways share interactions in one signaling network, and amplification-mediated deregulation of this network was found in 30.0% of these preinvasive lesions. No such alterations were found in 14 low-grade dysplasias that did not progress, whereas 43.5% (10/23) of OSCCs were found to have altered genes within the pathways with DNA amplification. Multitarget FISH showed that amplification of EGFR and CCND1 can coexist in single cells of an oral dysplasia, suggesting the dependence on multiple oncogenes for OPL progression. Taken together, these findings identify a critical biological network that is frequently disrupted in high-risk OPLs, with different specific genes disrupted in different individuals. (c) 2009 UICC.

Author information

Author/s: Tsui, Ivy F L (IF); Poh, Catherine F (CF); Garnis, Cathie (C); Rosin, Miriam P (MP); Zhang, Lewei (L); Lam, Wan L (WL);

Affiliation: Department of Cancer Genetics and Developmental Biology, British Columbia Cancer Research Centre, Vancouver, BC, Canada. itsui(-atsign-)bccrc.ca

Grants: R01 DE017013-04 (Agency:NIDCR NIH HHS) ; R01DE13124 (Agency:NIDCR NIH HHS) ; R01DE15965 (Agency:NIDCR NIH HHS)

Journal and publication information

Publication Type: Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't

Journal: International journal of cancer. Journal international du cancer (Int J Cancer), published in United States. (Language: eng)

Reference: 2009-Nov; vol 125 (issue 9) : pp 2219-28

Dates: Created 2009/09/03; Completed 2009/09/15; Revised 2009/11/03;

PMID: 19623652, status: MEDLINE (last retrieval date: 11/4/2009, IMS Date: )

Sourced from the National Library of Medicine. Abstract text and other information may be subject to copyright.

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MeSH headings (categories)

This article was linked to the MESH Headings shown below.

Carcinoma, Squamous Cell - genetics Cyclin D1 - genetics Fibroblast Growth Factors - physiology Gene Amplification Head and Neck Neoplasms - genetics Humans

Mouth Neoplasms - genetics Oligonucleotide Array Sequence Analysis Precancerous Conditions - genetics RNA, Messenger - analysis Receptor, Epidermal Growth Factor - genetics Signal Transduction - physiology

Associated Chemicals: CCND1 protein, human (0) ; RNA, Messenger (0) ; Cyclin D1 (136601-57-5) ; Fibroblast Growth Factors (62031-54-3) ; Receptor, Epidermal Growth Factor (EC 2.7.1.112)

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