Quantitative methylation profiles for multiple tumor suppressor gene promoters in salivary gland tumors

• Published in: PloS one Vol. 5; no. 5; p. e10828
• Main Authors: Durr, Megan L, Mydlarz, Wojciech K, Shao, Chunbo, Zahurak, Marianna L, Chuang, Alice Y, Hoque, Mohammad O, Westra, William H, Liegeois, Nanette J, Califano, Joseph A, Sidransky, David, Ha, Patrick K
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 26-05-2010; Public Library of Science (PLoS)
• Subjects: Adenomatous polyposis coli; Adolescent; Adult; Aged; Aged, 80 and over; Bladder cancer; Cancer; Cancer therapies; Deoxyribonucleic acid; Diagnostic software; Diagnostic systems; DNA; DNA methylation; DNA Methylation - genetics; DNA repair; Enzymes; Epigenetics; Esophagus; Female; Fluorescence; Genes; Head & neck cancer; Humans; Kinases; Male; Medical prognosis; Metastasis; Methylation; Middle Aged; Molecular Biology; Molecular Biology/DNA Methylation; Oncology; Oncology/Head and Neck Cancers; Oral cancer; Otolaryngology; Otolaryngology/Head and Neck Cancers; Otolaryngology/Head and Neck Surgery; Parotid gland; Polymerase Chain Reaction; Prognosis; Promoter Regions, Genetic; Promoters; Prostate cancer; Proteins; RNA polymerase; Salivary gland; Salivary Gland Neoplasms - genetics; Salivary Gland Neoplasms - pathology; Salivary Glands - metabolism; Salivary Glands - pathology; Statistical analysis; Studies; Surgery; Tissue inhibitor of metalloproteinase 3; Tumor suppressor genes; Tumor Suppressor Proteins - genetics; Tumor Suppressor Proteins - metabolism; Tumors; Urine; Young Adult; United States > US; Maryland; Baltimore Maryland
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0010828

Methylation profiling of tumor suppressor gene (TSGs) promoters is quickly becoming a powerful diagnostic tool for the early detection, prognosis, and even prediction of clinical response to treatment. Few studies address this in salivary gland tumors (SGTs); hence the promoter methylation profile of various TSGs was quantitatively assessed in primary SGT tissue to determine if tumor-specific alterations could be detected.
DNA isolated from 78 tumor and 17 normal parotid gland specimens was assayed for promoter methylation status of 19 TSGs by fluorescence-based, quantitative methylation-specific PCR (qMSP). The data were utilized in a binary fashion as well as quantitatively (using a methylation quotient) allowing for better profiling and interpretation of results.
The average number of methylation events across the studied genes was highest in salivary duct carcinoma (SDC), with a methylation value of 9.6, compared to the normal 4.5 (p<0.0003). There was a variable frequency and individual methylation quotient detected, depending on the TSG and the tumor type. When comparing normal, benign, and malignant SGTs, there was a statistically significant trend for increasing methylation in APC, Mint 1, PGP9.5, RAR-beta, and Timp3.
Screening promoter methylation profiles in SGTs showed considerable heterogeneity. The methylation status of certain markers was surprisingly high in even normal salivary tissue, confirming the need for such controls. Several TSGs were found to be associated with malignant SGTs, especially SDC. Further study is needed to evaluate the potential use of these associations in the detection, prognosis, and therapeutic outcome of these rare tumors.