CpG Island Hypermethylation in Human Colorectal Tumors Is Not Associated with DNA Methyltransferase Overexpression
作者： Peter V. Danenberg , Cindy A. Eads , Kathleen D. Danenberg , Kazuyuki Kawakami , Leonard B. Saltz
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摘要: The molecular basis of aberrant hypermethylation CpG islands observed in a subset human colorectal tumors is unknown. One potential mechanism the up-regulation DNA (cytosine-5)-methyltransferases. Recently, two new mammalian methyltransferase genes have been identified, which are referred to as DNMT3A and DNMT3B. encoded proteins differ from predominant DNMT1 that they substantially higher ratio de novo maintenance activity. We used highly quantitative 5' nuclease fluorogenic reverse transcription-PCR method (TaqMan) analyze expression all three 25 individual adenocarcinoma specimens matched normal mucosa samples. In addition, we examined methylation patterns four [APC, ESR1 (estrogen receptor), CDKN2A (p16), MLH1] determine whether show positive correlation between level frequency island hypermethylation. All methyltransferases appear be up-regulated when RNA levels normalized using either ACTB (beta-actin) or POLR2A (RNA pol II large subunit), but not with proliferation-associated genes, such H4F2 (histone H4) PCNA. extent did correlate any methyltransferases. Our results suggest deregulation gene does play role establishing tumor-specific abnormal cancer.
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