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Effect of ASXL1 on the stemness of colorectal cancer initiating cells.

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683Background: Impaired cellular differentiation causes uncontrolled proliferation of stem cells and can be a cause of oncogenesis. The epigenome regulates the expression of genes that are essential for cellular differentiation.… Click to show full abstract

683Background: Impaired cellular differentiation causes uncontrolled proliferation of stem cells and can be a cause of oncogenesis. The epigenome regulates the expression of genes that are essential for cellular differentiation. On the other hand, chromosomal abnormalities are common in colorectal cancer cells. We hypothesize that epigenetic disorders caused by chromosomal abnormalities may result in oncogenesis. Methods: The Cancer Genome Atlas (TCGA) database was investigated to identify epigenetic regulating genes affected by chromosomal abnormalities. Patient-derived colorectal cancer cells were obtained from consented patients to validate these findings. Results: The amplification of Chr20q11 is the most frequent chromosomal alteration in left-sided colonic and rectal cancers. ASXL1, a recruiter of PRC2, is coded in Chr20q11 and has upregulated expression in many cases. Excessive expression of ASXL1 may cause oncogenesis as PRC2 trimethylates histone H3 on lysine 27 (H3K27me3), an epigenetic mark of ...

Keywords: asxl1 stemness; colorectal cancer; stemness colorectal; chromosomal abnormalities; cancer; effect asxl1

Journal Title: Journal of Clinical Oncology
Year Published: 2018

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