Epigenetic "bivalently marked" process of cancer stem cell-driven tumorigenesis.
Silencing of tumor suppressor genes (TSGs), by DNA methylation, is well known in adult cancers. However, based on the "stem cell" theory of tumorigenesis, the early epigenetic events arising in malignant precursors remain unknown. A recent report demonstrates that, while pluripotent embryonic stem cells lack DNA methylation and possess a "bivalent" pattern of activating and repressive histone marks in numerous TSGs, analogous multipotent malignant cells derived from germ cell tumors (embryonic carcinoma cells) gain additional silencing modifications to those same genes. These results suggest a possible mechanism by which aberrant differentiation, mediated by histone and DNA methylation, instigates tumor progression.
Balch
Curt
C
Medical Sciences Program, Indiana University, Bloomington, IN, USA.
Nephew
Kenneth P
KP
Huang
Tim H-M
TH
Bapat
Sharmila A
SA
D000328:Adult; D002454:Cell Differentiation; D049109:Cell Proliferation; D002843:Chromatin / Q000378:metabolism; D053595:Embryonic Stem Cells / Q000502:physiology*; D044127:Epigenesis, Genetic; D015972:Gene Expression Regulation, Neoplastic; D020868:Gene Silencing; D016147:Genes, Tumor Suppressor; D006801:Humans; D009369:Neoplasms / Q000378:metabolism / Q000473:pathology; D063146:Polycomb-Group Proteins; D012097:Repressor Proteins / Q000235:genetics / Q000378:metabolism
D002843:Chromatin; D063146:Polycomb-Group Proteins; D012097:Repressor Proteins