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

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 o...

Full description

Bibliographic Details
Main Authors: Megan L Durr, Wojciech K Mydlarz, Chunbo Shao, Marianna L Zahurak, Alice Y Chuang, Mohammad O Hoque, William H Westra, Nanette J Liegeois, Joseph A Califano, David Sidransky, Patrick K Ha
Format: Article
Language:English
Published: Public Library of Science (PLoS) 2010-05-01
Series:PLoS ONE
Online Access:http://europepmc.org/articles/PMC2877085?pdf=render
_version_ 1818555494330007552
author Megan L Durr
Wojciech K Mydlarz
Chunbo Shao
Marianna L Zahurak
Alice Y Chuang
Mohammad O Hoque
William H Westra
Nanette J Liegeois
Joseph A Califano
David Sidransky
Patrick K Ha
author_facet Megan L Durr
Wojciech K Mydlarz
Chunbo Shao
Marianna L Zahurak
Alice Y Chuang
Mohammad O Hoque
William H Westra
Nanette J Liegeois
Joseph A Califano
David Sidransky
Patrick K Ha
author_sort Megan L Durr
collection DOAJ
description 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.
first_indexed 2024-12-12T09:54:11Z
format Article
id doaj.art-ac6e9c54c38641f4aa5ff3b9f06610a6
institution Directory Open Access Journal
issn 1932-6203
language English
last_indexed 2024-12-12T09:54:11Z
publishDate 2010-05-01
publisher Public Library of Science (PLoS)
record_format Article
series PLoS ONE
spelling doaj.art-ac6e9c54c38641f4aa5ff3b9f06610a62022-12-22T00:28:11ZengPublic Library of Science (PLoS)PLoS ONE1932-62032010-05-0155e1082810.1371/journal.pone.0010828Quantitative methylation profiles for multiple tumor suppressor gene promoters in salivary gland tumors.Megan L DurrWojciech K MydlarzChunbo ShaoMarianna L ZahurakAlice Y ChuangMohammad O HoqueWilliam H WestraNanette J LiegeoisJoseph A CalifanoDavid SidranskyPatrick K HaMethylation 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.http://europepmc.org/articles/PMC2877085?pdf=render
spellingShingle Megan L Durr
Wojciech K Mydlarz
Chunbo Shao
Marianna L Zahurak
Alice Y Chuang
Mohammad O Hoque
William H Westra
Nanette J Liegeois
Joseph A Califano
David Sidransky
Patrick K Ha
Quantitative methylation profiles for multiple tumor suppressor gene promoters in salivary gland tumors.
PLoS ONE
title Quantitative methylation profiles for multiple tumor suppressor gene promoters in salivary gland tumors.
title_full Quantitative methylation profiles for multiple tumor suppressor gene promoters in salivary gland tumors.
title_fullStr Quantitative methylation profiles for multiple tumor suppressor gene promoters in salivary gland tumors.
title_full_unstemmed Quantitative methylation profiles for multiple tumor suppressor gene promoters in salivary gland tumors.
title_short Quantitative methylation profiles for multiple tumor suppressor gene promoters in salivary gland tumors.
title_sort quantitative methylation profiles for multiple tumor suppressor gene promoters in salivary gland tumors
url http://europepmc.org/articles/PMC2877085?pdf=render
work_keys_str_mv AT meganldurr quantitativemethylationprofilesformultipletumorsuppressorgenepromotersinsalivaryglandtumors
AT wojciechkmydlarz quantitativemethylationprofilesformultipletumorsuppressorgenepromotersinsalivaryglandtumors
AT chunboshao quantitativemethylationprofilesformultipletumorsuppressorgenepromotersinsalivaryglandtumors
AT mariannalzahurak quantitativemethylationprofilesformultipletumorsuppressorgenepromotersinsalivaryglandtumors
AT aliceychuang quantitativemethylationprofilesformultipletumorsuppressorgenepromotersinsalivaryglandtumors
AT mohammadohoque quantitativemethylationprofilesformultipletumorsuppressorgenepromotersinsalivaryglandtumors
AT williamhwestra quantitativemethylationprofilesformultipletumorsuppressorgenepromotersinsalivaryglandtumors
AT nanettejliegeois quantitativemethylationprofilesformultipletumorsuppressorgenepromotersinsalivaryglandtumors
AT josephacalifano quantitativemethylationprofilesformultipletumorsuppressorgenepromotersinsalivaryglandtumors
AT davidsidransky quantitativemethylationprofilesformultipletumorsuppressorgenepromotersinsalivaryglandtumors
AT patrickkha quantitativemethylationprofilesformultipletumorsuppressorgenepromotersinsalivaryglandtumors