Abstract

We have described a preliminary genetic progression model that describes the timing of specific genetic events in head and neck squamous cell carcinoma progression. This model has included the nature and timing of loss and amplification at specific chromosomal loci that contain putative tumor suppressor genes and proto-oncogenes, respectively. Specific tumor suppressor genes, including p14 and p16, and proto-oncogenes, including p63, have been identified as critical in oral cancer development. This study builds upon the foundation of this prior model by identifying specific, ordered transcriptional alterations in order to establish a transcriptional progression model of oral cancer. The transcriptome of oral SCC described by this model will be correlated with DNA based SNP analysis to map and identify putative oncogenes and tumor suppressor genes. Specific attention will be directed at identification of early transcriptional and genetic alterations. These early molecular events will be identified and developed as targets for early detection and staging approaches, with emphasis on molecular detection strategies amenable to rapid, automated application.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of Dental & Craniofacial Research (NIDCR)
Type
Method to Extend Research in Time (MERIT) Award (R37)
Project #
5R37DE012588-14
Application #
8213646
Study Section
Special Emphasis Panel (ZRG1-CG (01))
Program Officer
Venkatachalam, Sundaresan
Project Start
1998-04-01
Project End
2014-02-28
Budget Start
2012-03-01
Budget End
2014-02-28
Support Year
14
Fiscal Year
2012
Total Cost
$393,723
Indirect Cost
$153,648

  Institution

Name
Johns Hopkins University
Department
Otolaryngology
Type
Schools of Medicine
DUNS #
001910777
City
Baltimore
State
MD
Country
United States
Zip Code
21218

  Publications

Izumchenko, Evgeny; Chang, Xiaofei; Michailidi, Christina et al. (2014) The TGF?-miR200-MIG6 pathway orchestrates the EMT-associated kinase switch that induces resistance to EGFR inhibitors. Cancer Res 74:3995-4005
Mydlarz, Wojciech; Uemura, Mamoru; Ahn, Sun et al. (2014) Clusterin is a gene-specific target of microRNA-21 in head and neck squamous cell carcinoma. Clin Cancer Res 20:868-77
Demokan, Semra; Chuang, Alice Y; Chang, Xiaofei et al. (2013) Identification of guanine nucleotide-binding protein ýý-7 as an epigenetically silenced gene in head and neck cancer by gene expression profiling. Int J Oncol 42:1427-36
Chang, Xiaofei; Izumchenko, Eugene; Solis, Luisa M et al. (2013) The relative expression of Mig6 and EGFR is associated with resistance to EGFR kinase inhibitors. PLoS One 8:e68966
Hidalgo, Manuel; Bruckheimer, Elizabeth; Rajeshkumar, N V et al. (2011) A pilot clinical study of treatment guided by personalized tumorgrafts in patients with advanced cancer. Mol Cancer Ther 10:1311-6
Agrawal, Nishant; Frederick, Mitchell J; Pickering, Curtis R et al. (2011) Exome sequencing of head and neck squamous cell carcinoma reveals inactivating mutations in NOTCH1. Science 333:1154-7
Guerrero-Preston, R; Soudry, E; Acero, J et al. (2011) NID2 and HOXA9 promoter hypermethylation as biomarkers for prevention and early detection in oral cavity squamous cell carcinoma tissues and saliva. Cancer Prev Res (Phila) 4:1061-72
Chang, Xiaofei; Monitto, Constance L; Demokan, Semra et al. (2010) Identification of hypermethylated genes associated with cisplatin resistance in human cancers. Cancer Res 70:2870-9
Smith, Ian M; Mithani, Suhail K; Mydlarz, Wojciech K et al. (2010) Inactivation of the tumor suppressor genes causing the hereditary syndromes predisposing to head and neck cancer via promoter hypermethylation in sporadic head and neck cancers. ORL J Otorhinolaryngol Relat Spec 72:44-50
Chatterjee, Aditi; Chang, Xiaofei; Sen, Tanusree et al. (2010) Regulation of p53 family member isoform DeltaNp63alpha by the nuclear factor-kappaB targeting kinase IkappaB kinase beta. Cancer Res 70:1419-29

Showing the most recent 10 out of 13 publications