Quantitative promoter methylation analysis of multiple cancer-related genes in renal cell tumors

<p>Abstract</p> <p>Background</p> <p>Aberrant promoter hypermethylation of cancer-associated genes occurs frequently during carcinogenesis and may serve as a cancer biomarker. In this study we aimed at defining a quantitative gene promoter methylation panel that might i...

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Main Authors: Oliveira Jorge, Pinto Mafalda, Ribeiro Franclim R, Henrique Rui, Costa Vera L, Lobo Francisco, Teixeira Manuel R, Jerónimo Carmen
Format: Article
Language:English
Published: BMC 2007-07-01
Series:BMC Cancer
Online Access:http://www.biomedcentral.com/1471-2407/7/133
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author Oliveira Jorge
Pinto Mafalda
Ribeiro Franclim R
Henrique Rui
Costa Vera L
Lobo Francisco
Teixeira Manuel R
Jerónimo Carmen
author_facet Oliveira Jorge
Pinto Mafalda
Ribeiro Franclim R
Henrique Rui
Costa Vera L
Lobo Francisco
Teixeira Manuel R
Jerónimo Carmen
author_sort Oliveira Jorge
collection DOAJ
description <p>Abstract</p> <p>Background</p> <p>Aberrant promoter hypermethylation of cancer-associated genes occurs frequently during carcinogenesis and may serve as a cancer biomarker. In this study we aimed at defining a quantitative gene promoter methylation panel that might identify the most prevalent types of renal cell tumors.</p> <p>Methods</p> <p>A panel of 18 gene promoters was assessed by quantitative methylation-specific PCR (QMSP) in 85 primarily resected renal tumors representing the four major histologic subtypes (52 clear cell (ccRCC), 13 papillary (pRCC), 10 chromophobe (chRCC), and 10 oncocytomas) and 62 paired normal tissue samples. After genomic DNA isolation and sodium bisulfite modification, methylation levels were determined and correlated with standard clinicopathological parameters.</p> <p>Results</p> <p>Significant differences in methylation levels among the four subtypes of renal tumors were found for <it>CDH1 </it>(<it>p </it>= 0.0007), <it>PTGS2 </it>(<it>p </it>= 0.002), and <it>RASSF1A </it>(<it>p </it>= 0.0001). <it>CDH1 </it>hypermethylation levels were significantly higher in ccRCC compared to chRCC and oncocytoma (<it>p </it>= 0.00016 and <it>p </it>= 0.0034, respectively), whereas <it>PTGS2 </it>methylation levels were significantly higher in ccRCC compared to pRCC (<it>p </it>= 0.004). <it>RASSF1A </it>methylation levels were significantly higher in pRCC than in normal tissue (<it>p </it>= 0.035). In pRCC, <it>CDH1 </it>and <it>RASSF1A </it>methylation levels were inversely correlated with tumor stage (<it>p </it>= 0.031) and nuclear grade (<it>p </it>= 0.022), respectively.</p> <p>Conclusion</p> <p>The major subtypes of renal epithelial neoplasms display differential aberrant <it>CDH1</it>, <it>PTGS2</it>, and <it>RASSF1A </it>promoter methylation levels. This gene panel might contribute to a more accurate discrimination among common renal tumors, improving preoperative assessment and therapeutic decision-making in patients harboring suspicious renal masses.</p>
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spelling doaj.art-0c263a2ebd784808b405517f0cafe6482022-12-22T02:50:49ZengBMCBMC Cancer1471-24072007-07-017113310.1186/1471-2407-7-133Quantitative promoter methylation analysis of multiple cancer-related genes in renal cell tumorsOliveira JorgePinto MafaldaRibeiro Franclim RHenrique RuiCosta Vera LLobo FranciscoTeixeira Manuel RJerónimo Carmen<p>Abstract</p> <p>Background</p> <p>Aberrant promoter hypermethylation of cancer-associated genes occurs frequently during carcinogenesis and may serve as a cancer biomarker. In this study we aimed at defining a quantitative gene promoter methylation panel that might identify the most prevalent types of renal cell tumors.</p> <p>Methods</p> <p>A panel of 18 gene promoters was assessed by quantitative methylation-specific PCR (QMSP) in 85 primarily resected renal tumors representing the four major histologic subtypes (52 clear cell (ccRCC), 13 papillary (pRCC), 10 chromophobe (chRCC), and 10 oncocytomas) and 62 paired normal tissue samples. After genomic DNA isolation and sodium bisulfite modification, methylation levels were determined and correlated with standard clinicopathological parameters.</p> <p>Results</p> <p>Significant differences in methylation levels among the four subtypes of renal tumors were found for <it>CDH1 </it>(<it>p </it>= 0.0007), <it>PTGS2 </it>(<it>p </it>= 0.002), and <it>RASSF1A </it>(<it>p </it>= 0.0001). <it>CDH1 </it>hypermethylation levels were significantly higher in ccRCC compared to chRCC and oncocytoma (<it>p </it>= 0.00016 and <it>p </it>= 0.0034, respectively), whereas <it>PTGS2 </it>methylation levels were significantly higher in ccRCC compared to pRCC (<it>p </it>= 0.004). <it>RASSF1A </it>methylation levels were significantly higher in pRCC than in normal tissue (<it>p </it>= 0.035). In pRCC, <it>CDH1 </it>and <it>RASSF1A </it>methylation levels were inversely correlated with tumor stage (<it>p </it>= 0.031) and nuclear grade (<it>p </it>= 0.022), respectively.</p> <p>Conclusion</p> <p>The major subtypes of renal epithelial neoplasms display differential aberrant <it>CDH1</it>, <it>PTGS2</it>, and <it>RASSF1A </it>promoter methylation levels. This gene panel might contribute to a more accurate discrimination among common renal tumors, improving preoperative assessment and therapeutic decision-making in patients harboring suspicious renal masses.</p>http://www.biomedcentral.com/1471-2407/7/133
spellingShingle Oliveira Jorge
Pinto Mafalda
Ribeiro Franclim R
Henrique Rui
Costa Vera L
Lobo Francisco
Teixeira Manuel R
Jerónimo Carmen
Quantitative promoter methylation analysis of multiple cancer-related genes in renal cell tumors
BMC Cancer
title Quantitative promoter methylation analysis of multiple cancer-related genes in renal cell tumors
title_full Quantitative promoter methylation analysis of multiple cancer-related genes in renal cell tumors
title_fullStr Quantitative promoter methylation analysis of multiple cancer-related genes in renal cell tumors
title_full_unstemmed Quantitative promoter methylation analysis of multiple cancer-related genes in renal cell tumors
title_short Quantitative promoter methylation analysis of multiple cancer-related genes in renal cell tumors
title_sort quantitative promoter methylation analysis of multiple cancer related genes in renal cell tumors
url http://www.biomedcentral.com/1471-2407/7/133
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