癌抑制遺伝子の異常なエピジェネティックサイレンシングをダイレクトリプログラミングで戻した

エルサレム・ヘブライ大学のAmir Edenらのグループによって、癌抑制遺伝子であるp16（CDKN2A）の異常なエピジェネティックサイレンシングがダイレクトリプログラミングによって復帰し、p16発現が回復したという論文が発表されました。

分化後もp16発現は安定的に維持されたとのこと。

Stem Cells. 2010 Jun 22. [Epub ahead of print]

Aberrant Epigenetic Silencing of Tumor Suppressor Genes is Reversed by Direct Reprogramming.
Ron-Bigger S, Bar-Nur O, Isaac S, Bocker M, Lyko F, Eden A.
http://www.ncbi.nlm.nih.gov/pubmed/20572015?dopt=Abstract

Direct reprogramming procedures reset the epigenetic memory of cells and convert differentiated somatic cells into pluripotent stem cells (iPS cells). In addition to epigenetic memory of cell identity, which is established during development, somatic cells can accumulate abnormal epigenetic changes which can contribute to pathological conditions. Aberrant promoter hypermethylation and epigenetic silencing of tumor suppressor genes are now recognized as an important mechanism in tumor initiation and progression. Here we have studied the fate of the silenced tumor suppressor gene p16(CDKN2A) during direct reprogramming. We find that following reprogramming, p16 expression is restored and is stably maintained even when cells are induced to differentiate. Large scale methylation profiling of donor cells identified aberrant methylation at hundreds of additional sites. Methylation at many, but not all these sites was reversed following reprogramming. Our results suggest that reprogramming approaches may be applied to repair the epigenetic lesions associated with cancer.