Molecular and Genomic Profiling of Head and Neck Tumors

Previous research by our group using genetic microarray analysis of HNSCC and normal
keratinocytes has identified two distinct groups of genetic expression based on clustering
patterns of a subgroup of genes. Clinical data was summarized for each group and overall,
patient segregation by gene expression profiling was a better predictor of outcome than
clinicopathological variables. Further analysis identified 375 genes that discriminate
between the genotypic subtypes of HNSCC. Overall, our preliminary data has shown that the
pattern of global gene expression in a HNSCC specimen can be used as a predictor of
prognosis. We isolated subsets of genes showing the greatest patterns of divergence in gene
expression. We have also identified 366 over-expressed and 246 underexpressed genes when
comparing primary tumor to normal surgical margins and have identified a similar number of
genes whose expression has changed when comparing primary tumor to lymph node metastasis.
Combining these data sets we have identified genes which consistently increase or decrease
expression during progression from normal tissue to primary tumor, and subsequently to
metastatic node. We have selected several candidate genes for subsequent analysis using HNSCC
tissue arrays. Through DNA microarray analysis and other techniques for looking at genetic
and molecular characteristics, a more detailed knowledge of the malignant transformation
process, and alterations with therapy, in these patients may be obtained. This study will
seek to perform comprehensive molecular and genetic profiling to improve biomarker
development in HNSCC and correlate this data with patient clinical data. Ultimately it is
hoped that tumor specific genetic abnormalities may be identified which could provide targets
for treatment strategies such as gene therapy, immunotherapy, or other interventions.

Study Objectives:

To evaluate gene expression patterns in human head and neck squamous cell carcinoma and
correlate this with treatment response, both surgical and non-surgical.

To identify a series of diagnostic markers in blood, urine and/or sputum for head and neck
squamous cell carcinoma and study the mechanism of action of these proteins.

Inclusion Criteria:

- actual or suspected malignant or non-malignant tumors of the head and neck

- planned biopsy and/or resection, or availability of paraffin embedded or stored frozen
tumor tissue for non-genetic analysis

Exclusion Criteria:

- insufficient tissue available for both standard diagnostic evaluation and study
specimen