DNA methylation-associated repression of cancer-germline genes in human embryonic and adult stem cells.
Cancer-germline (CG) genes are a particular group of germline-specific genes that rely primarily on DNA methylation for repression in somatic tissues. In a wide variety of tumors, the promoter of these genes is demethylated, and their transcription is activated. The mechanism underlying this tumor-specific activation is still unclear. It was recently suggested that CG gene expression may be a hallmark of stem cells, and that expression of these genes in several tumors may reflect the expansion of constitutively expressing cancer stem cells. To clarify this issue, we carefully evaluated the expression of several CG genes in human stem cells of embryonic and adult origin. We found no or very weak expression of CG genes in these cells. Consistently, the promoter of CG genes was highly methylated in these cells. We conclude that CG genes do not qualify as "stemness" genes, and propose that their activation in cancers results from a tumor-specific activation process.
Cellular Genetics Unit, de Duve Institute, Université Catholique de Louvain, Brussels, Belgium.
Axelle
A
Loriot
Sven
S
Reister
Gregory K
GK
Parvizi
Philippe A
PA
Lysy
Charles
C
De Smet
D053687:Adult Stem Cells / Q000502:physiology*; D000951:Antigens, Neoplasm / Q000235:genetics*; D002460:Cell Line; D019175:DNA Methylation; D004622:Embryo, Mammalian / Q000166:cytology / Q000502:physiology; D053595:Embryonic Stem Cells / Q000502:physiology*; D005786:Gene Expression Regulation; D052138:Genes, Neoplasm; D006801:Humans; D014411:Neoplastic Stem Cells / Q000502:physiology; D011401:Promoter Regions, Genetic; D020133:Reverse Transcriptase Polymerase Chain Reaction
D000951:Antigens, Neoplasm