Details

Autor(en) / Beteiligte

• Kimple, Randall J.
• Blitzer, Grace C.
• Torres, Alexandra D.
• Yang, Robert Z.
• Lorenz, Laurel D.
• Armstrong, Eric A.
• Soriano, Benjamin J.
• Lambert, Paul F.
• Harari, Paul M.

Titel

Abstract 2352: Molecular profiles of head and neck cancer tumorgrafts

Ist Teil von

• Cancer research (Chicago, Ill.), 2012-04, Vol.72 (8_Supplement), p.2352-2352

Erscheinungsjahr

2012

Quelle

EZB Electronic Journals Library

Beschreibungen/Notizen

• Abstract Purpose: We have developed a primary tumorgraft system of squamous cell carcinoma of the head and neck with relevance for investigating mechanisms of therapeutic resistance, understanding differential responses to standard therapy in HPV-positive and HPV-negative cancers, and testing novel therapeutics. To better understand the power, limitations and relevance of our tumorgraft system, we have initiated molecular characterization of these tumors. Methods: Patients with newly diagnosed or recurrent HNSCC were consented for donation of tumor at the time of surgery. Tumor tissue was obtained, washed in antibiotic rich media, manually disaggregated, and subcutaneously implanted into mice (NOD.Cg-Prkdc scid Il2rgtm1Wjl/SzJ) for initial tumorgraft establishment. Subsequent mouse-to-mouse passages were performed and formalin-fixed/paraffin embedded as well as flash frozen tissue was harvested for subsequent molecular analyses. Expression of p16(Ink4a), p53, pRB, and EGFR was assessed by immunohistochemistry(IHC). HPV status and subtype was assessed using MY09/MY11 and GP5/GP6 degenerate nested polymerase chain reaction and Sanger sequencing. Transcriptionally active HPV infection was assessed by qRT-PCR for the HPV oncogenes E6 and E7. Mutation status of p53 was assessed by PCR-based exon amplification and Sanger sequencing. Results: To date, thirty primary tumorgrafts have been established with robust growth in eighteen (60%). p16(INK4A) expression was identified in approximately one-third. The majority of HPV-positive tumorgrafts contained HPV-16 and were transcriptionally active by mRNA expression profiling. HPV-positive tumors showed low p53 and RB expression by IHC. As anticipated, mutations in p53 were seen more frequently in HPV-negative tumors. Conclusions: These primary human tumorgrafts represent a diverse range of head and neck cancers. Both HPV-positive tumors and HPV-negative tumors have been successfully propagated with a diverse range of molecular characteristics. These primary tumorgrafts will provide a valuable platform for testing novel therapeutics as well as radiation and chemotherapy response profiles. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 2352. doi:1538-7445.AM2012-2352