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`Promoter Methylation Precedes Chromosomal Alterations in Colorectal Cancer Development - PMC
`
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`
`C O : O J
`I S C O
`
`Hindawi Limited
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`Cell Oncol. 2006; 28(5-6): 247–257.
`Published online 2006 Dec 12. doi: 10.1155/2006/846251
`
`PMCID: PMC4618222
`PMID: 17167178
`
`Sarah Derks, Cindy Postma, Peter T. M. Moerkerk, Sandra M. van den Bosch, Beatriz Carvalho,
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`Mario A. J. A. Hermsen, Walter Giaretti, James G. Herman, Matty P. Weijenberg, Adriaan P. de Bruïne,
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`Gerrit A. Meijer, and Manon van Engeland
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`Promoter Methylation Precedes Chromosomal Alterations in Colorectal Cancer
`Development
`Abstract
`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 chro-
`mosomal alterations in colorectal carcinogenesis. Methods: In a series of 47 nonprogressed ade-
`nomas, 41 progressed adenomas (malignant polyps), 38 colorectal carcinomas and 18 paired nor-
`mal tissues, we evaluated promoter methylation status of hMLH1, O MGMT, APC, p14
`RASSF1A, GATA-4, GATA-5, and CHFR using methylation-speciic PCR. Mutation status of TP53, APC
`and KRAS were studied by p53 immunohistochemistry and sequencing of the APC and KRAS muta-
`tion cluster regions. Chromosomal alterations were evaluated by comparative genomic hybridiza-
`tion. Results: Our data demonstrate that nonprogressed adenomas, progressed adenomas and car-
`cinomas show similar frequencies of promoter methylation for the majority of the genes. Normal
`tissues showed signiicantly lower frequencies of promoter methylation of APC, p16
`, 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 ade-
`nomas 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.
`Keywords: Colorectal cancer, promoter methylation, genetic alterations, chromosomal instability
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`6
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`ARF
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`, p16
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`INK4A
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`INK4A
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`https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4618222/
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`1/9/24, 12:10 PM
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`Promoter Methylation Precedes Chromosomal Alterations in Colorectal Cancer Development - PMC
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`https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4618222/
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`Geneoscopy Exhibit 1041, Page 2
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