Associate Professor, Department of Pathology
Head and neck squamous cell carcinomas (HNSCC) constitute an anatomically heterogenous group of neoplasms that share in common a causal association with tobacco and alcohol exposure. The clinical course of these neoplasms is difficult to predict based on established prognostic clinicopathological criteria. Unfortunately, the 5-year survival rate has improved only marginally over the past decade; as a result, it is estimated that over 45,000 cases and over 11,000 deaths will occur each year in the United States from HNSCC. To date, there are few molecular markers that can be reliably used in either early detection or as indicators of prognosis.
Evidence has now established that aberrant DNA methylation and chromatin remodeling associated with promoters, or first exons of genes, is one mechanism frequently associated with the transcriptional silencing of critical genes in HNSCC and other cancers. One goal of our lab is the genome-wide analysis of aberrant DNA methylation events in head and neck tumor genomes. These “epigenetic signatures” can be used to identify CpG island sequences frequently hypermethylated in HNSCC, and to characterize previously indistinguishable subtypes of this disease. The long-term goal of our research is to identify genetic and epigenetic signatures associated with successful treatment and patient outcome in this disease, as well as those signatures that indicate that drug treatment will not work. This should lead to more unique gene discoveries and, in the future, new targets for anti-tumor drugs.
Belbin TJ, Singh,B, Barber I, Socci N, Wenig B, Smith R, Prystowsky M, Childs G. Molecular classification of head and neck squamous cell carcinoma using cDNA microarrays (2002). Cancer Res 62:1184-1190.
Wreesman VB, Sieczka E, Socci ND, Hezel M, Belbin TJ, Childs G, Patel SG, Patel KN, Tallini G, Prystowsky MB, Shaha AR, Kraus D, Shah JP, Rao PH, Ghossein R, Singh B. Genome-wide profiling of papillary thyroid cancer identifies MUC1 as an independent prognostic marker (2004). Cancer Res 64:3780-3789.
Childs G, Fazzari M, Kung G, Kawachi N, Brandwein-Gensler M, McLemore M, Chen Q, Burk RD, Smith RV, Prystowsky MB, Belbin TJ, Schlecht NF (2009). Low-level expression of microRNAs let-7d and miR-205 are prognostic markers of head and neck squamous cell carcinoma. Am J Pathol. 174(3):736-745.
Lleras RA, Adrien LR, Smith RV, Sarta C, Schlecht NF, Harris TM, Childs G, Prystowsky MB, Belbin TJ (2011). Hypermethylation of a cluster of Krüppel-type zinc finger protein genes on chromosome 19q13 in oropharyngeal squamous cell carcinoma. Am. J. Pathol. 178(5): 1965-1974.
Belbin TJ, Lleras RA, Smith RV, Schlecht NF, Lim J, Harris TM, Childs G, Prystowsky MB. “Capturing and deciphering the molecular signatures of head and neck cancer.” In Cancer Genomics - Molecular classification, prognosis and response prediction (Ulrich Pfeffer, Ed.). Springer Press, 2013.
Lleras RA, Smith RV, Adrien LR, Schlecht NF, Burk RD, Harris TM, Childs G, Prystowsky MB, Belbin TJ (2013). Unique DNA Methylation Loci Distinguish Anatomic Site and HPV Status in Head and Neck Squamous Cell Carcinoma. Clin. Cancer Res. (In Press).
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Albert Einstein College of Medicine
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