TY - JOUR
T1 - Methylation of cancer-stem-cell-associated Wnt target genes predicts poor prognosis in colorectal cancer patients
AU - de Sousa E Melo, Felipe
AU - Colak, Selcuk
AU - Buikhuisen, Joyce
AU - Koster, Jan
AU - Cameron, Kate
AU - de Jong, Joan H.
AU - Tuynman, Jurriaan B.
AU - Prasetyanti, Pramudita R.
AU - Fessler, Evelyn
AU - van den Bergh, Saskia P.
AU - Rodermond, Hans
AU - Dekker, Evelien
AU - van der Loos, Chris M.
AU - Pals, Steven T.
AU - van de Vijver, Marc J.
AU - Versteeg, Rogier
AU - Richel, Dick J.
AU - Vermeulen, Louis
AU - Medema, Jan Paul
PY - 2011
Y1 - 2011
N2 - Gene signatures derived from cancer stem cells (CSCs) predict tumor recurrence for many forms of cancer. Here, we derived a gene signature for colorectal CSCs defined by high Wnt signaling activity, which in agreement with previous observations predicts poor prognosis. Surprisingly, however, we found that elevated expression of Wnt targets was actually associated with good prognosis, while patient tumors with low expression of Wnt target genes segregated with immature stem cell signatures. We discovered that several Wnt target genes, including ASCL2 and LGR5, become silenced by CpG island methylation during progression of tumorigenesis, and that their re-expression was associated with reduced tumor growth. Taken together, our data show that promoter methylation of Wnt target genes is a strong predictor for recurrence of colorectal cancer, and suggest that CSC gene signatures, rather than reflecting CSC numbers, may reflect differentiation status of the malignant tissue
AB - Gene signatures derived from cancer stem cells (CSCs) predict tumor recurrence for many forms of cancer. Here, we derived a gene signature for colorectal CSCs defined by high Wnt signaling activity, which in agreement with previous observations predicts poor prognosis. Surprisingly, however, we found that elevated expression of Wnt targets was actually associated with good prognosis, while patient tumors with low expression of Wnt target genes segregated with immature stem cell signatures. We discovered that several Wnt target genes, including ASCL2 and LGR5, become silenced by CpG island methylation during progression of tumorigenesis, and that their re-expression was associated with reduced tumor growth. Taken together, our data show that promoter methylation of Wnt target genes is a strong predictor for recurrence of colorectal cancer, and suggest that CSC gene signatures, rather than reflecting CSC numbers, may reflect differentiation status of the malignant tissue
U2 - https://doi.org/10.1016/j.stem.2011.10.008
DO - https://doi.org/10.1016/j.stem.2011.10.008
M3 - Article
C2 - 22056143
SN - 1934-5909
VL - 9
SP - 476
EP - 485
JO - Cell Stem Cell
JF - Cell Stem Cell
IS - 5
ER -