Volume 139, Issue 6, Pages (December 2010)

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Volume 139, Issue 6, Pages 1855-1864 (December 2010) Hypomethylation of the IGF2 DMR in Colorectal Tumors, Detected by Bisulfite Pyrosequencing, Is Associated With Poor Prognosis Yoshifumi Baba, Katsuhiko Nosho, Kaori Shima, Curtis Huttenhower, Noriko Tanaka, Aditi Hazra, Edward L. Giovannucci, Charles S. Fuchs, Shuji Ogino Gastroenterology Volume 139, Issue 6, Pages 1855-1864 (December 2010) DOI: 10.1053/j.gastro.2010.07.050 Copyright © 2010 AGA Institute Terms and Conditions

Figure 1 IGF2 DMR0 methylation levels in colorectal cancer and normal mucosa. (A) Representative pyrograms in IGF2 DMR0 methylation assay. The top panel shows a tumor with high methylation level (47.5%), and the bottom panel shows a tumor with low methylation level (13.3%). The percentage numbers (in blue shade) are proportions of C and T at each CpG site after bisulfite conversion, and the proportion of C indicates the methylation level at each CpG site. The second and third CpG sites follow stretches of Ts leading to apparently high T peaks relative to C peaks. (B) IGF2 DMR0 methylation levels in 51 colorectal cancers and matched normal mucosa. Cancer tissues showed a significantly lower level of methylation (mean, 31.9; median, 29.7) than matched normal mucosa (mean, 50.6; median, 51.4) (P < .0001 by the paired t test). Gastroenterology 2010 139, 1855-1864DOI: (10.1053/j.gastro.2010.07.050) Copyright © 2010 AGA Institute Terms and Conditions

Figure 2 IGF2 DMR0 methylation levels in colorectal cancer. (A) Distribution of IGF2 DMR0 methylation levels in 1105 colorectal cancers. (B) Significant correlation between IGF2 DMR0 methylation level and LINE-1 methylation level in colorectal cancer (r = 0.29; P < .0001). Gastroenterology 2010 139, 1855-1864DOI: (10.1053/j.gastro.2010.07.050) Copyright © 2010 AGA Institute Terms and Conditions

Figure 3 Kaplan–Meier curves for colorectal cancer–specific survival (top panels) and overall survival (bottom panels) according to quartiles (Q1–4) of IGF2 DMR0 methylation level in colorectal cancer. On the right panels, Q4 represents the hypomethylated group, and Q1, Q2, and Q3 represent the hypermethylated group. Gastroenterology 2010 139, 1855-1864DOI: (10.1053/j.gastro.2010.07.050) Copyright © 2010 AGA Institute Terms and Conditions