Abstract

The purpose of this study is to delineate the molecular anatomy of mitochondrial genetic changes in head and neck cancer development. Mitochondrial mutations and genetic alterations have been found in head and neck cancer and mitochondrial dysfunction, DNA damage, and apoptotic dysregulation are found in multiple solid tumors. The entire 16 KB mitochondrial genome will be tested using conventional PCR based and novel array based sequencing assays in primary head and neck cancers and premalignant lesions. These alterations will be placed in the context of a genetic progression model for head and neck cancer to determine mitochondrial alterations that occur early in progression. Identified or engineered mutations in cell lines will be tested to understand their impact on mitochondrial biology and their role in cancer progression. Ultimately, identified mitochondrial alterations will be used as markers for molecular detection approaches using a novel, fluorescence based gap ligase chain reaction assay. ? ?

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of Dental & Craniofacial Research (NIDCR)
Type
Research Project (R01)
Project #
5R01DE015939-03
Application #
7010344
Study Section
Special Emphasis Panel (ZDE1-PZ (15))
Program Officer
Shirazi, Yasaman
Project Start
2004-04-01
Project End
2008-02-28
Budget Start
2006-03-01
Budget End
2008-02-28
Support Year
3
Fiscal Year
2006
Total Cost
$399,144
Indirect Cost

  Institution

Name
Johns Hopkins University
Department
Otolaryngology
Type
Schools of Medicine
DUNS #
001910777
City
Baltimore
State
MD
Country
United States
Zip Code
21218

  Publications

Zaboli, David; Tan, Marietta; Gogineni, Hrishikesh et al. (2012) Hyperfractionated radiotherapy with concurrent cisplatin/5-Fluorouracil for locoregional advanced head and neck cancer: analysis of 105 consecutive patients. Int J Otolaryngol 2012:754191
Smith, Ian M; Mithani, Suhail K; Mydlarz, Wojciech K et al. (2010) Inactivation of the tumor suppressor genes causing the hereditary syndromes predisposing to head and neck cancer via promoter hypermethylation in sporadic head and neck cancers. ORL J Otorhinolaryngol Relat Spec 72:44-50
Chuang, Tony C Y; Chuang, Alice Y C; Poeta, Luana et al. (2010) Detectable BRAF mutation in serum DNA samples from patients with papillary thyroid carcinomas. Head Neck 32:229-34
Glazer, Chad A; Chang, Steven S; Ha, Patrick K et al. (2009) Applying the molecular biology and epigenetics of head and neck cancer in everyday clinical practice. Oral Oncol 45:440-6
Mithani, Suhail K; Shao, Chunbo; Tan, Marietta et al. (2009) Mitochondrial mutations in adenoid cystic carcinoma of the salivary glands. PLoS One 4:e8493
Ha, Patrick K; Chang, Steven S; Glazer, Chad A et al. (2009) Molecular techniques and genetic alterations in head and neck cancer. Oral Oncol 45:335-9
Smith, Ian M; Mithani, Suhail K; Liu, Chunyan et al. (2009) Novel integrative methods for gene discovery associated with head and neck squamous cell carcinoma development. Arch Otolaryngol Head Neck Surg 135:487-95
Sun, Wenyue; Zhou, Shaoyu; Chang, Steven S et al. (2009) Mitochondrial mutations contribute to HIF1alpha accumulation via increased reactive oxygen species and up-regulated pyruvate dehydrogenease kinase 2 in head and neck squamous cell carcinoma. Clin Cancer Res 15:476-84
Chuang, Alice Y; Chuang, Tony C; Chang, Steven et al. (2008) Presence of HPV DNA in convalescent salivary rinses is an adverse prognostic marker in head and neck squamous cell carcinoma. Oral Oncol 44:915-9
Zhao, Ming; Begum, Shahnaz; Ha, Patrick K et al. (2008) Downregulation of RAD17 in head and neck cancer. Head Neck 30:35-42

Showing the most recent 10 out of 29 publications