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The Two-Hit Hypothesis Meets Epigenetics
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DOI：10.1158/0008-5472.CAN-22-0405.png)
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摘要
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The landmark paper by Kane and colleagues was the first report of DNA methylation in the promoter of the human MLH1 gene in sporadic colon cancers with mismatch repair (MMR) deficiency. In both cell lines and primary tumors, promoter methylation was associated with loss of MLH1 protein expression and with a lack of mutations in the MLH1 coding region. Together with subsequent papers that showed that this methylation was directly responsible for loss of MLH1 expression and MMR deficiency, the observation expanded the two-hit hypothesis of tumor suppressor gene loss in cancer to include both genetic and epigenetic mechanisms of gene inactivation. More broadly, the paper contributed to normalization of the hypothesis of an epigenetic basis for cancer development.
Keyword:
METHYLATION
HMLH1
期刊
IF:
16.6
论文数:
10.9W
被引数:
11.9W
机构
引用论文
Incidence and functional consequences of hMLH1 promoter hypermethylation in colorectal carcinoma
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OAAI分享收藏分享收藏Fusobacterium in Colonic Flora and Molecular Features of Colorectal Carcinoma.png)
CANCER RESEARCHOAAI
CANCER RESEARCHIF16.6
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