Promoter Methylation Precedes Chromosomal Alterations in Colorectal Cancer Development
Background: Colorectal cancers are characterized by genetic and epigenetic alterations. This study aimed to explore the timing of promoter methylation and relationship with mutations and chromosomal alterations in colorectal carcinogenesis. Methods: In a series of 47 nonprogressed adenomas, 41 progr...
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| Main Authors: | , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Wiley
2006-01-01
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| Series: | Cellular Oncology |
| Online Access: | http://dx.doi.org/10.1155/2006/846251 |
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| author | Sarah Derks Cindy Postma Peter T. M. Moerkerk Sandra M. van den Bosch Beatriz Carvalho Mario A. J. A. Hermsen Walter Giaretti James G. Herman Matty P. Weijenberg Adriaan P. de Bruïne Gerrit A. Meijer Manon van Engeland |
| author_facet | Sarah Derks Cindy Postma Peter T. M. Moerkerk Sandra M. van den Bosch Beatriz Carvalho Mario A. J. A. Hermsen Walter Giaretti James G. Herman Matty P. Weijenberg Adriaan P. de Bruïne Gerrit A. Meijer Manon van Engeland |
| author_sort | Sarah Derks |
| collection | DOAJ |
| description | Background: Colorectal cancers are characterized by genetic and epigenetic alterations. This study aimed to explore the timing of promoter methylation and relationship with mutations and chromosomal alterations in colorectal carcinogenesis. Methods: In a series of 47 nonprogressed adenomas, 41 progressed adenomas (malignant polyps), 38 colorectal carcinomas and 18 paired normal tissues, we evaluated promoter methylation status of hMLH1, O6MGMT, APC, p14ARF, p16INK4A, RASSF1A, GATA-4, GATA-5, and CHFR using methylation-specific PCR. Mutation status of TP53, APC and KRAS were studied by p53 immunohistochemistry and sequencing of the APC and KRAS mutation cluster regions. Chromosomal alterations were evaluated by comparative genomic hybridization. Results: Our data demonstrate that nonprogressed adenomas, progressed adenomas and carcinomas show similar frequencies of promoter methylation for the majority of the genes. Normal tissues showed significantly lower frequencies of promoter methylation of APC, p16INK4A, GATA-4, and GATA-5 (P-values: 0.02, 0.02, 1.1×10−5 and 0.008 respectively). P53 immunopositivity and chromosomal abnormalities occur predominantly in carcinomas (P values: 1.1×10−5 and 4.1×10−10). Conclusions: Since promoter methylation was already present in nonprogressed adenomas without chromosomal alterations, we conclude that promoter methylation can be regarded as an early event preceding TP53 mutation and chromosomal abnormalities in colorectal cancer development. |
| format | Article |
| id | doaj-art-6197e484961441bebbc8ce10a2d9e3e8 |
| institution | Kabale University |
| issn | 1570-5870 1875-8606 |
| language | English |
| publishDate | 2006-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Cellular Oncology |
| spelling | doaj-art-6197e484961441bebbc8ce10a2d9e3e82025-02-03T06:11:45ZengWileyCellular Oncology1570-58701875-86062006-01-01285-624725710.1155/2006/846251Promoter Methylation Precedes Chromosomal Alterations in Colorectal Cancer DevelopmentSarah Derks0Cindy Postma1Peter T. M. Moerkerk2Sandra M. van den Bosch3Beatriz Carvalho4Mario A. J. A. Hermsen5Walter Giaretti6James G. Herman7Matty P. Weijenberg8Adriaan P. de Bruïne9Gerrit A. Meijer10Manon van Engeland11Department of Pathology, Research Institute GROW, University Maastricht, The NetherlandsDepartment of Pathology, VU University Medical Center, Amsterdam, The NetherlandsDepartment of Pathology, Research Institute GROW, University Maastricht, The NetherlandsDepartment of Pathology, Research Institute GROW, University Maastricht, The NetherlandsDepartment of Pathology, VU University Medical Center, Amsterdam, The NetherlandsDept. of Otolaryngology, Instituto Universitario de Oncología del Principado de Asturias (IUOPA), Hospital Central de Asturias, Oviedo, SpainDepartment of Oncogenesis, Biophysics and Cytometry, National Institute for Cancer Research, Genoa, ItalyDepartment of Tumor Biology, The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore, Maryland, USADepartment of Epidemiology, Nutrition and Toxicology, Research Institute NUTRIM, University Maastricht, The NetherlandsDepartment of Pathology, Research Institute GROW, University Maastricht, The NetherlandsDepartment of Pathology, VU University Medical Center, Amsterdam, The NetherlandsDepartment of Pathology, Research Institute GROW, University Maastricht, The NetherlandsBackground: Colorectal cancers are characterized by genetic and epigenetic alterations. This study aimed to explore the timing of promoter methylation and relationship with mutations and chromosomal alterations in colorectal carcinogenesis. Methods: In a series of 47 nonprogressed adenomas, 41 progressed adenomas (malignant polyps), 38 colorectal carcinomas and 18 paired normal tissues, we evaluated promoter methylation status of hMLH1, O6MGMT, APC, p14ARF, p16INK4A, RASSF1A, GATA-4, GATA-5, and CHFR using methylation-specific PCR. Mutation status of TP53, APC and KRAS were studied by p53 immunohistochemistry and sequencing of the APC and KRAS mutation cluster regions. Chromosomal alterations were evaluated by comparative genomic hybridization. Results: Our data demonstrate that nonprogressed adenomas, progressed adenomas and carcinomas show similar frequencies of promoter methylation for the majority of the genes. Normal tissues showed significantly lower frequencies of promoter methylation of APC, p16INK4A, GATA-4, and GATA-5 (P-values: 0.02, 0.02, 1.1×10−5 and 0.008 respectively). P53 immunopositivity and chromosomal abnormalities occur predominantly in carcinomas (P values: 1.1×10−5 and 4.1×10−10). Conclusions: Since promoter methylation was already present in nonprogressed adenomas without chromosomal alterations, we conclude that promoter methylation can be regarded as an early event preceding TP53 mutation and chromosomal abnormalities in colorectal cancer development.http://dx.doi.org/10.1155/2006/846251 |
| spellingShingle | Sarah Derks Cindy Postma Peter T. M. Moerkerk Sandra M. van den Bosch Beatriz Carvalho Mario A. J. A. Hermsen Walter Giaretti James G. Herman Matty P. Weijenberg Adriaan P. de Bruïne Gerrit A. Meijer Manon van Engeland Promoter Methylation Precedes Chromosomal Alterations in Colorectal Cancer Development Cellular Oncology |
| title | Promoter Methylation Precedes Chromosomal Alterations in Colorectal Cancer Development |
| title_full | Promoter Methylation Precedes Chromosomal Alterations in Colorectal Cancer Development |
| title_fullStr | Promoter Methylation Precedes Chromosomal Alterations in Colorectal Cancer Development |
| title_full_unstemmed | Promoter Methylation Precedes Chromosomal Alterations in Colorectal Cancer Development |
| title_short | Promoter Methylation Precedes Chromosomal Alterations in Colorectal Cancer Development |
| title_sort | promoter methylation precedes chromosomal alterations in colorectal cancer development |
| url | http://dx.doi.org/10.1155/2006/846251 |
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