We will spend the next grant period on epigenetic marks in lung cancer that will build on our previous work on unmasking promoter methylation (Aim 3). We will extend our promoter work to extensively study hypomethylated promoters with a subsequent increase in gene expression for incorporation into EDRN collaborations that focus on RNA or protein (Aim 2). We will assess global methylation status in lung cancer cell lines and primary lung tumors and use new tiled arrays to identify genome-wide regions of methylation (Aim 1). These studies will thus be complementary to our ongoing studies using pharmacologic unmasking and will allow direct comparison between genes methylated in tumors of unclear significance and those that are reactivated after 5-AZA treatment, suggesting a more functional role in tumor progression. Once identified, we will use the assays we developed including MSP and QMSP to test regions of promoter hypermethylation to develop measurable biomarkers. These assays will allow continuing to develop highly specific and sensitive tests to detect tumor cells in various bodily fluids such as serum, plasma, sputum, and BAL fluid for early detection and diagnosis. We have also designed a novel QD-FRET nanoprobe technology for detecting nucleic acids and an additional approach here will be to build these probes for specific methylation markers we discover and validate. The proposed integrated program has the ability to achieve this goal because it optimally applies existing investigator talent, achievement, and interest using the most promising current research directions in epigenetics.

Public Health Relevance

This proposal will comprehensively identify a variety of epigenetic markers in lung cancer. All the proposed aims are unite around the common research goal of generating and applying new molecular markers for the eariy detection and diagnosis of lung cancer. In this way, the morbidity and mortality of this deadly disease may be diminished by eariy and timely detection with appropriate therapy.

Agency
National Institute of Health (NIH)
Type
Research Project--Cooperative Agreements (U01)
Project #
3U01CA084986-15S1
Application #
8843674
Study Section
Special Emphasis Panel (ZCA1)
Program Officer
Lin, Alison J
Project Start
Project End
Budget Start
Budget End
Support Year
15
Fiscal Year
2014
Total Cost
Indirect Cost
Name
Johns Hopkins University
Department
Otolaryngology
Type
Schools of Medicine
DUNS #
City
Baltimore
State
MD
Country
United States
Zip Code
21218
Izumchenko, Evgeny; Chang, Xiaofei; Brait, Mariana et al. (2015) Targeted sequencing reveals clonal genetic changes in the progression of early lung neoplasms and paired circulating DNA. Nat Commun 6:8258
Izumchenko, Evgeny; Sun, Kai; Jones, Sian et al. (2015) Notch1 mutations are drivers of oral tumorigenesis. Cancer Prev Res (Phila) 8:277-86
Begum, Shahnaz; Hayashi, Masamichi; Ogawa, Takenori et al. (2015) An integrated genome-wide approach to discover deregulated microRNAs in non-small cell lung cancer: Clinical significance of miR-23b-3p deregulation. Sci Rep 5:13236
Bateman, Nicholas W; Jaworski, Elizabeth; Ao, Wei et al. (2015) Elevated AKAP12 in paclitaxel-resistant serous ovarian cancer cells is prognostic and predictive of poor survival in patients. J Proteome Res 14:1900-10
Kagohara, Luciane Tsukamoto; Schussel, Juliana L; Subbannayya, Tejaswini et al. (2015) Global and gene-specific DNA methylation pattern discriminates cholecystitis from gallbladder cancer patients in Chile. Future Oncol 11:233-49
Cherny, Nathan I; de Vries, Elisabeth G E; Emanuel, Linda et al. (2014) Words matter: distinguishing "personalized medicine" and "biologically personalized therapeutics". J Natl Cancer Inst 106:
Guerrero-Preston, Rafael; Hadar, Tal; Ostrow, Kimberly Laskie et al. (2014) Differential promoter methylation of kinesin family member 1a in plasma is associated with breast cancer and DNA repair capacity. Oncol Rep 32:505-12
Guerrero-Preston, Rafael; Ogawa, Takenori; Uemura, Mamoru et al. (2014) Cold atmospheric plasma treatment selectively targets head and neck squamous cell carcinoma cells. Int J Mol Med 34:941-6
Guo, Mingzhou; Jia, Yan; Yu, Zhengtao et al. (2014) Epigenetic changes associated with neoplasms of the exocrine and endocrine pancreas. Discov Med 17:67-73
Brebi, Priscilla; Maldonado, Leonel; Noordhuis, Maartje G et al. (2014) Genome-wide methylation profiling reveals Zinc finger protein 516 (ZNF516) and FK-506-binding protein 6 (FKBP6) promoters frequently methylated in cervical neoplasia, associated with HPV status and ethnicity in a Chilean population. Epigenetics 9:308-17

Showing the most recent 10 out of 141 publications