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


METHODS
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.


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.


CONCLUSIONS
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.
Department of Otolaryngology-Head and Neck Surgery, Johns Hopkins Medical Institution, Baltimore, Maryland, USA.
Megan L
ML
Durr
Wojciech K
WK
Mydlarz
Chunbo
C
Shao
Marianna L
ML
Zahurak
Alice Y
AY
Chuang
Mohammad O
MO
Hoque
William H
WH
Westra
Nanette J
NJ
Liegeois
Joseph A
JA
Califano
David
D
Sidransky
Patrick K
PK
Ha
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D019175:DNA Methylation / Q000235:genetics*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D016133:Polymerase Chain Reaction; D011401:Promoter Regions, Genetic; D012468:Salivary Gland Neoplasms / Q000235:genetics* / Q000473:pathology*; D012469:Salivary Glands / Q000378:metabolism / Q000473:pathology; D025521:Tumor Suppressor Proteins / Q000235:genetics* / Q000378:metabolism; D055815:Young Adult
D025521:Tumor Suppressor Proteins