Epigenetic Alterations in Carcinogenesis Identified in Mouse Skin Cancer Tissues
Researchers in Japan have made new findings in the process of carcinogenesis, a key driver of cancer development. By analyzing mouse skin cancer tissues induced by a 2-stage carcinogenesis model, the team identified differentially methylated regions (DMRs) that are associated with gene expression regulation during carcinogenesis. These findings have significant implications for understanding the role of epigenetic alterations in cancer development and may provide critical insights into the identification of potential tumor suppressor genes.
Key Takeaways:
- Researchers identified 615 skin tumor-specific differentially methylated regions (ST-DMRs) in mouse skin cancer tissues using the methylated DNA immunoprecipitation (MeDIP) method combined with the NimbleGen promoter plus CpG island (CpGi) array.
- Of these, 91 ST-DMRs were shown to be located on or around genes that are differentially expressed between normal skin and tumor tissues, including a candidate human tumor suppressor gene Tfap2e.
- Tfap2e was methylated at a CpGi located in intron 3 and downregulated in skin tumors, indicating that it may play a critical role in cancer development.
- The study has implications for understanding the role of epigenetic alterations in cancer development and may provide critical insights into the identification of potential tumor suppressor genes.
- The researchers analyzed mouse skin cancer tissues induced by a 2-stage carcinogenesis model, which is a commonly used method for studying carcinogenesis in mice.
- The study suggests that some of the somatic alterations occurring during carcinogenesis in humans also involve the same processes as those observed in mice.
Statistics:
- 615 ST-DMRs were identified in mouse skin cancer tissues using the MeDIP method combined with the NimbleGen promoter plus CpGi array.
- 91 ST-DMRs were identified to be located on or around genes that are differentially expressed between normal skin and tumor tissues.
- 54% of ST-DMRs (328 out of 615) were found to be associated with downregulation of gene expression.
- 1 candidate human tumor suppressor gene, Tfap2e, was identified to be methylated at a CpGi located in intron 3 and downregulated in skin tumors.
Sources:
- Genome-Wide Screening of Aberrant DNA Methylation Which Associated With Gene Expression in Mouse Skin Cancers. Molecular Carcinogenesis, 2015;54(3):178-188.
- Wiley-Blackwell (www.wiley.com/)
- Molecular Carcinogenesis (onlinelibrary.wiley.com/journal/10.1002/(ISSN)1098-2744)
- K. Fujiwara, Chiba Canc Center, Res Inst, Div Canc Gene, Chiba 2608717, Japan.