Abstract

Salivary gland malignancies represent only 1-2% of all head and neck malignancies in the United States. Their behavior can be quite variable, and treatment usually involves surgery and radiation therapy. Because not much is known about the molecular mechanisms of these unusual tumors, chemotherapy and other targeted therapies have not been shown to be effective. As part of this collaborative proposal, our aim is to evaluate the role of promoter methylation as a means of tumor suppressor gene silencing using new microarray technology. We intend to use the Illumina Human Methylation27 array which is able to sample the methylation status of over 14,000 genes. We can then validate the identified targets and go on to perform further mechanistic studies of their biologic relevance in these malignancies. Performing this comprehensive analysis will allow us to determine the effect of epigenetic silencing on the carcinogenesis of salivary gland cancers.

Public Health Relevance

The goal of this grant is to help identify the significance of methyaltion in salivary gland cancers with the hopes of providing either therapeutic targets or markers for disease that can be used for prognosis or screening.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of Dental & Craniofacial Research (NIDCR)
Type
Research Project--Cooperative Agreements (U01)
Project #
5U01DE019765-04
Application #
8288813
Study Section
Special Emphasis Panel (ZRG1-HOP-Y (50))
Program Officer
Atkinson, Jane C
Project Start
2009-09-20
Project End
2014-05-31
Budget Start
2012-06-01
Budget End
2013-05-31
Support Year
4
Fiscal Year
2012
Total Cost
$1,275,931
Indirect Cost
$438,011

  Institution

Name
University of Texas MD Anderson Cancer Center
Department
Pathology
Type
Other Domestic Higher Education
DUNS #
800772139
City
Houston
State
TX
Country
United States
Zip Code
77030

  Publications

Saintigny, Pierre; Mitani, Yoshitsugu; Pytynia, Kristen B et al. (2018) Frequent PTEN loss and differential HER2/PI3K signaling pathway alterations in salivary duct carcinoma: Implications for targeted therapy. Cancer 124:3693-3705
Gudmundsson, Julius; Thorleifsson, Gudmar; Sigurdsson, Jon K et al. (2017) A genome-wide association study yields five novel thyroid cancer risk loci. Nat Commun 8:14517
Liu, Bin; Mitani, Yoshitsugu; Rao, Xiayu et al. (2017) Spatio-Temporal Genomic Heterogeneity, Phylogeny, and Metastatic Evolution in Salivary Adenoid Cystic Carcinoma. J Natl Cancer Inst 109:
Chen, Diane Wenhua; Lewin, Jan S; Xu, Li et al. (2017) Feeding Tube Utilization in Patients with Salivary Gland Malignancies. Otolaryngol Head Neck Surg 156:109-117
Ferrarotto, Renata; Mitani, Yoshitsugu; Diao, Lixia et al. (2017) Activating NOTCH1 Mutations Define a Distinct Subgroup of Patients With Adenoid Cystic Carcinoma Who Have Poor Prognosis, Propensity to Bone and Liver Metastasis, and Potential Responsiveness to Notch1 Inhibitors. J Clin Oncol 35:352-360
Mitani, Yoshitsugu; Liu, Bin; Rao, Pulivarthi H et al. (2016) Novel MYBL1 Gene Rearrangements with Recurrent MYBL1-NFIB Fusions in Salivary Adenoid Cystic Carcinomas Lacking t(6;9) Translocations. Clin Cancer Res 22:725-33
Wang, Zhiming; Ling, Shizhang; Rettig, Eleni et al. (2015) Epigenetic screening of salivary gland mucoepidermoid carcinoma identifies hypomethylation of CLIC3 as a common alteration. Oral Oncol 51:1120-5
Xu, Li; Tang, Hongwei; Chen, Diane W et al. (2015) Genome-wide association study identifies common genetic variants associated with salivary gland carcinoma and its subtypes. Cancer 121:2367-74
Xu, Li; Tang, Hongwei; El-Naggar, Adel K et al. (2015) Genetic variants in DNA double-strand break repair genes and risk of salivary gland carcinoma: a case-control study. PLoS One 10:e0128753
Bell, Diana; Hanna, Ehab Y; Miele, Lucio et al. (2014) Expression and significance of notch signaling pathway in salivary adenoid cystic carcinoma. Ann Diagn Pathol 18:10-3

Showing the most recent 10 out of 39 publications