Early detection of cancer of the mouth and throat (head and neck squamous cell carcinoma [HNSCC]) wouldresult in substantial improvement in survival for the 40,000 Americans diagnosed with this disease each yearwhile reducing morbidity associated with treatment, Changes in DNA that underly tumorigenesis are idealmolecular markers for highly sensitive and specific approaches to early detection. We have had promisingresults in pilot projects for detection of HNSCC in oral rinses (saliva) and serum of affected individuals usinghypermethylation markers identified during the first funding period by Project 1. In the proposed new fundingperiod, it is anticipated that the number of promising markers identified in Project 1 will double or triple . Inorder to produce an accurate, useful and cost-effective detection test, it will be necessary to combinemarkers that have shown initial promise into detection panels. However, the presence of some markers insaliva and serum of healthy control subjects requires that detection panels be compartment specific.We willassemble and verify candidate markers and panels through the assessment of tumor-specifichypermethylation of promoter regions in tumors, premalignant lesions, exfoliated cells in oral rinsespecimens, and serum. Quantitative methylations specific PCR which is amenable to high-throughputapplication will be employed. The prevelance of alterations in sets of tumors will be assessed, followed byevaluation of the presence of identical markers in clinical specimens (saliva and serum). Simple sensitivityand specificity estimates will be explored in various panel combinations. The proposed panels of markerswillthen be tested in samples from subjects enrolled in premalignant and post-treatment surveillance studies(aims 2 and 3). Subjects will be recruited at the Johns Hopkins Medical Institutions and the MD AndersonCancer Center. The utility of marker panels for detection and prediction of recurrence/progression will beexplored.

Agency
National Institute of Health (NIH)
Institute
National Institute of Dental & Craniofacial Research (NIDCR)
Type
Specialized Center (P50)
Project #
9P50DE019032-06
Application #
7300558
Study Section
Special Emphasis Panel (ZCA1-GRB-I (M1))
Project Start
2007-06-01
Project End
2012-05-31
Budget Start
2007-09-17
Budget End
2008-07-31
Support Year
6
Fiscal Year
2007
Total Cost
$308,938
Indirect Cost
Name
Johns Hopkins University
Department
Type
DUNS #
001910777
City
Baltimore
State
MD
Country
United States
Zip Code
21218
Kelley, Dylan Z; Flam, Emily L; Guo, Theresa et al. (2018) Functional characterization of alternatively spliced GSN in head and neck squamous cell carcinoma. Transl Res 202:109-119
Ghantous, Yasmine; Schussel, Juliana L; Brait, Mariana (2018) Tobacco and alcohol-induced epigenetic changes in oral carcinoma. Curr Opin Oncol 30:152-158
Gleber-Netto, Frederico O; Zhao, Mei; Trivedi, Sanchit et al. (2018) Distinct pattern of TP53 mutations in human immunodeficiency virus-related head and neck squamous cell carcinoma. Cancer 124:84-94
Kagohara, Luciane T; Stein-O'Brien, Genevieve L; Kelley, Dylan et al. (2018) Epigenetic regulation of gene expression in cancer: techniques, resources and analysis. Brief Funct Genomics 17:49-63
Windon, Melina J; D'Souza, Gypsyamber; Rettig, Eleni M et al. (2018) Increasing prevalence of human papillomavirus-positive oropharyngeal cancers among older adults. Cancer 124:2993-2999
Ravi, Rajani; Noonan, Kimberly A; Pham, Vui et al. (2018) Bifunctional immune checkpoint-targeted antibody-ligand traps that simultaneously disable TGF? enhance the efficacy of cancer immunotherapy. Nat Commun 9:741
Bishop, Justin A; Westra, William H (2018) MYB Translocation Status in Salivary Gland Epithelial-Myoepithelial Carcinoma: Evaluation of Classic, Variant, and Hybrid Forms. Am J Surg Pathol 42:319-325
Pai, Sara I; Jack Lee, J; Carey, Thomas E et al. (2018) HLA class I antigen processing machinery (APM) component expression and PD-1:PD-L1 pathway activation in HIV-infected head and neck cancers. Oral Oncol 77:92-97
Bishop, Justin A; Rooper, Lisa M; Chiosea, Simion I et al. (2018) Clear Cell Carcinoma of Salivary Glands Is Frequently p16 Positive: A Pitfall in the Interpretation of Oropharyngeal Biopsies. Am J Surg Pathol 42:367-371
Afsari, Bahman; Guo, Theresa; Considine, Michael et al. (2018) Splice Expression Variation Analysis (SEVA) for inter-tumor heterogeneity of gene isoform usage in cancer. Bioinformatics 34:1859-1867

Showing the most recent 10 out of 137 publications