Squamous cell carcinoma of the oral cavity and oropharynx is the 6th most common cancer worldwide. The overall 5-year survival rates for oral cancer have remained low at approximately 30-40% for the past decades and has remain among the worst of all cancer death rates, considerably lower than that for colorectal, cervix and breast origin. Significant improvement of functional mapping is needed to move the oral cancer diagnosis, treatment and research forward.

Our genetic discovery project aims to identify the concordant alterations at genomic and transcriptional levels for oral squamous cell carcinoma (SCC). The rationale is that ultimate impact of genomic abnormalities is exerted by altered expression of encoded genes. However, not all observed genomic alterations have a functional impact and/or are required for oral/head and neck SCC development. On the other hand, some
expression alterations may represent secondary adaptive responses and/or non-specific responses, instead of real functional contribution to cancer development. These limitations complicate the search for robust biomarkers and functional candidate genes and point to the need for combining genomic and expressional strategies. Our approach is to decipher the molecular determinants of oral/head and neck SCC using the concordant genomic and transcriptional analysis. The advantages of this type of synergistic approach are significant. If the same gene shows DNA copy number abnormalities and altered expression, not only do we have independent validation of the profiling data but we will also have determined the mechanism of altered expression of that gene. Furthermore, that particular gene will be more likely to have biological significance. Our immediate goal is to establish the comparative genomic and expression profiles at critical tumorigenesis stages of oral SCC development. In particular, our current research projects are to identify concordant
genomic and expressional alterations contribute to 1) the progression of oral premalignant lesion to oral SCC, and 2) the conversion of non-metastasis oral SCC to metastasis SCC. Our goal is to identify a set of genetic alterations and/or candidate genes that have high functional relevance to oral squamous cell carcinoma development. Microarray based differential expression technology and high density SNP array-based genetic typing technologies are utilized.


Funding

RO1 DE015970-01 (Wong)
NIH/NIDCR
Genomics and Proteomics of Oral Precancer Progression

13KT-0028 (Zhou)
Tobacco Related Disease Research Program (TRDRP)
Genomics and Transcriptome of Oral Precancer Progression in Smokers

K22 DE014847-01(Zhou)
NIH/NIDCR
Genomic Predictors of Oral Premalignancy Progression

RO3 DE016569-01(Zhou)
NIH/NIDCR
Expression-based identification of OHNC genomic changes

RO3 CA114688-01(Zhou)
NIH/NCI
Molecular Determinants of Oral Cancer Detection


Publications

1. X. Zhou, S.W. Cole, S. Hu, and D.T. Wong. Detection of DNA copy number abnormality by microarray expression analysis. Hum Genet (2004) 114(5):464-467

2. X. Zhou, C. Li, S.C. Mok, Z. Chen, and D.T. Wong. Whole genome loss of heterozygosity profiling on oral squamous cell carcinoma by high-density single nucleotide polymorphic allele (SNP) array. Cancer Genet Cytogen (2004) 151(1):82-84.

3. X. Zhou, R.C.K. Jordan, S.C. Mok, M.J. Birrer, and D.T. Wong. DNA copy number abnormality of oral squamous cell carcinoma detected by cDNA array-based CGH. Cancer Genet Cytogen (2004) 151(1):90-92.

4. X. Zhou, S.C. Mok, Z. Chen, Y. Li and D.T. Wong. Concurrent analysis of loss of heterozygosity (LOH) and copy number abnormality (CNA) for oral premalignancy progression using Affymetrix 10K SNP mapping array. Hum Genet (2004) 115(4):327-30.

5.  X. Zhou, S.C. Mok, N.P. Rao, Z. Cheng, S.W. Cole, D.T. Wong. Progress in concurrent analysis of loss of heterozygosity and comparative genomic hybridization utilizing high density single nucleotide polymorphism arrays. Cancer Genet Cytogen (2005) 159(1):53-7.

6. X. Zhou, S.W. Cole, N.P. Rao, Z. Chen, Y. Li, J. McBride, and D.T.Wong. Identification of discrete chromosomal deletion by binary recursive partitioning of microarray differential expression data. J Med Genet (2005) 42(5):416-419.

7.  X. Zhou, R.C.K. Jordan, Y. Li, B.L. Huang, and D.T. Wong. Frequent allelic imbalance at 8p and 11q22 in oral cavity and oropharyngeal epithelial dysplastic lesions. Cancer Genet Cytogen (2005) 161(1):86-9.