Outlier analysis defines zinc finger gene family DNA methylation in tumors and saliva of head and neck cancer patients

Daria Gaykalova, Rajita Vatapalli, Yingying Wei, Hua Ling Tsai, Hao Wang, Chi Zhang, Patrick T. Hennessey, Theresa Guo, Marietta Tan, Ryan Li, Julie Ahn, Zubair Khan, William H. Westra, Justin A. Bishop, David Zaboli, Wayne Martin Koch, Tanbir Khan, Michael F. Ochs, Joseph A. Califano

Research output: Contribution to journalArticle

Abstract

Head and Neck Squamous Cell Carcinoma (HNSCC) is the fifth most common cancer, annually affecting over half a million people worldwide. Presently, there are no accepted biomarkers for clinical detection and surveillance of HNSCC. In this work, a comprehensive genome-wide analysis of epigenetic alterations in primary HNSCC tumors was employed in conjunction with cancer-specific outlier statistics to define novel biomarker genes which are differentially methylated in HNSCC. The 37 identified biomarker candidates were top-scoring outlier genes with prominent differential methylation in tumors, but with no signal in normal tissues. These putative candidates were validated in independent HNSCC cohorts from our institution and TCGA (The Cancer Genome Atlas). Using the top candidates, ZNF14, ZNF160, and ZNF420, an assay was developed for detection of HNSCC cancer in primary tissue and saliva samples with 100% specificity when compared to normal control samples. Given the high detection specificity, the analysis of ZNF DNA methylation in combination with other DNA methylation biomarkers may be useful in the clinical setting for HNSCC detection and surveillance, particularly in high-risk patients. Several additional candidates identified through this work can be further investigated toward future development of a multi-gene panel of biomarkers for the surveillance and detection of HNSCC.

Original languageEnglish (US)
Article numbere0142148
JournalPLoS One
Volume10
Issue number11
DOIs
StatePublished - Nov 6 2015

Fingerprint

zinc finger motif
Zinc Fingers
squamous cell carcinoma
DNA methylation
DNA Methylation
Head and Neck Neoplasms
saliva
Saliva
neck
Zinc
Tumors
Genes
Biomarkers
neoplasms
biomarkers
Neoplasms
genes
monitoring
Genome
Tissue

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

Cite this

Outlier analysis defines zinc finger gene family DNA methylation in tumors and saliva of head and neck cancer patients. / Gaykalova, Daria; Vatapalli, Rajita; Wei, Yingying; Tsai, Hua Ling; Wang, Hao; Zhang, Chi; Hennessey, Patrick T.; Guo, Theresa; Tan, Marietta; Li, Ryan; Ahn, Julie; Khan, Zubair; Westra, William H.; Bishop, Justin A.; Zaboli, David; Koch, Wayne Martin; Khan, Tanbir; Ochs, Michael F.; Califano, Joseph A.

In: PLoS One, Vol. 10, No. 11, e0142148, 06.11.2015.

Research output: Contribution to journalArticle

Gaykalova, D, Vatapalli, R, Wei, Y, Tsai, HL, Wang, H, Zhang, C, Hennessey, PT, Guo, T, Tan, M, Li, R, Ahn, J, Khan, Z, Westra, WH, Bishop, JA, Zaboli, D, Koch, WM, Khan, T, Ochs, MF & Califano, JA 2015, 'Outlier analysis defines zinc finger gene family DNA methylation in tumors and saliva of head and neck cancer patients', PLoS One, vol. 10, no. 11, e0142148. https://doi.org/10.1371/journal.pone.0142148
Gaykalova, Daria ; Vatapalli, Rajita ; Wei, Yingying ; Tsai, Hua Ling ; Wang, Hao ; Zhang, Chi ; Hennessey, Patrick T. ; Guo, Theresa ; Tan, Marietta ; Li, Ryan ; Ahn, Julie ; Khan, Zubair ; Westra, William H. ; Bishop, Justin A. ; Zaboli, David ; Koch, Wayne Martin ; Khan, Tanbir ; Ochs, Michael F. ; Califano, Joseph A. / Outlier analysis defines zinc finger gene family DNA methylation in tumors and saliva of head and neck cancer patients. In: PLoS One. 2015 ; Vol. 10, No. 11.
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