DNA Analysis of Tumor Tissue Samples From Patients With Human Papilloma Virus-Associated Cancer of the Oropharynx

Study Overview
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Brief Summary
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RATIONALE: Studying samples of tumor tissue in the laboratory from patients with cancer may help doctors learn more about changes that occur in DNA and identify biomarkers related to cancer. PURPOSE: This laboratory study is looking at the DNA in tumor tissue samples from patients with human papilloma virus-associated cancer of the oropharynx.

Detailed Description
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OBJECTIVES: Analyze PIK3CA expression and mutation and p110α amplification and expression in tumor tissue samples from patients with human papilloma virus positive (HPV+) and human papilloma virus negative (HPV-) squamous cell carcinoma (SCC) of the oropharynx. Determine proliferation and survival after PI3K inhibition in HPV(+) and HPV(-) oropharyngeal SCC cell lines and in HPV E6 and E7 expressing cells. Determine proliferation and survival after PI3K inhibition in short-term cultures of tumor tissue samples from patients with HPV(+) and HPV(-) primary SCC of the oropharynx. OUTLINE: Previously collected tumor tissue samples are analyzed for HPV DNA by PCR amplification and direct sequencing of PCR products; expression of E6 protein and relative expression of PIK3CA by qRT-PCR; amplification of PIK3CA by Southern blotting; mutation of PIK3CA; expression of p110α, phospho-AKT, total AKT, and FOXO1 by polyacrylamide gel electrophoresis (PAGE) and immunoblotting; and the effect of PI3K inhibition on cell cycle and apoptosis by flow cytometry. Pharmacological studies are performed on oropharyngeal squamous cell carcinoma cell lines and short-term cultures and HPV E6 and E7 expressing cells using LY 294002 in vitro to analyze response to PI3K inhibition. Results of response to PI3K inhibition will be correlated with HPV status, PIK3CA expression, amplification, and mutation, and p110α expression. PROJECTED ACCRUAL: A total of 20 HPV(+) and 20 HPV(-) tumor tissue specimens from patients will be accrued for this study.

Official Title
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Effect of PI3K Inhibition in HPV-Associated HNSCC

Conditions
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Head and Neck Cancer

Intervention / Treatment
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* Genetic: gene expression analysis
* Genetic: mutation analysis
* Genetic: polyacrylamide gel electrophoresis
* Genetic: polymerase chain reaction
* Genetic: protein expression analysis
* Genetic: reverse transcriptase-polymerase chain reaction
* Other: flow cytometry
* Other: immunoenzyme technique
* Other: immunologic technique
* Other: laboratory biomarker analysis
* Other: pharmacological study


Participation Criteria
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Eligibility Criteria
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DISEASE CHARACTERISTICS: Undergoing operative procedures for biopsy and/or resection of squamous cell carcinoma (SCC) of the oropharynx Tumor tissue sample available from the Head and Neck Tissue Repository and Clinical Database of Vanderbilt University No tumors with human papilloma virus (HPV) DNA sequences but no expression of E6 PATIENT CHARACTERISTICS: See Disease Characteristics PRIOR CONCURRENT THERAPY: Not specified

Ages Eligible for Study
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Maximum Age: 120 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Intervention/Treatment |
| --- |
|Genetic: gene expression analysis|nan|
|Genetic: mutation analysis|nan|
|Genetic: polyacrylamide gel electrophoresis|nan|
|Genetic: polymerase chain reaction|nan|
|Genetic: protein expression analysis|nan|
|Genetic: reverse transcriptase-polymerase chain reaction|nan|
|Other: flow cytometry|nan|
|Other: immunoenzyme technique|nan|
|Other: immunologic technique|nan|
|Other: laboratory biomarker analysis|nan|
|Other: pharmacological study|nan|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| PIK3CA expression and mutation and p110α amplification and expression in tumor tissue samples from patients with human papilloma virus positive (HPV+) and human papilloma virus negative (HPV-) squamous cell carcinoma (SCC) of the oropharynx |  |  | 
| Proliferation and survival after PI3K inhibition in HPV(+) and HPV(-) oropharyngeal SCC cell lines and in HPV E6 and E7 expressing cells |  |  | 
| Proliferation and survival after PI3K inhibition in short-term cultures of tumor tissues from patients with HPV(+) and HPV(-) primary SCC of the oropharynx |  |  | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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recurrent squamous cell carcinoma of the oropharynx, stage I squamous cell carcinoma of the oropharynx, stage II squamous cell carcinoma of the oropharynx, stage III squamous cell carcinoma of the oropharynx, stage IV squamous cell carcinoma of the oropharynx