Loss of imprinting in normal tissue of colorectal cancer patients with microsatellite instability

Abstract

Loss of imprinting (LOI) is an epigenetic alteration of some cancers involving loss of parental origin-specific expression of imprinted genes. We observed LOI of the insulin-like growth factor-II gene in twelve of twenty-seven informative colorectal cancer patients (44%), as well as in the matched normal colonic mucosa of the patients with LOI in their cancers, and in peripheral blood samples of four patients. Ten of eleven cancers (91%) with microsatellite instability showed LOI, compared with only two of sixteen tumors (12%) without microsatellite instability ( P < 0.001). Control patients without cancer showed LOI in colonic mucosa of only two of sixteen cases (12%, P < 0.001) and two of fifteen blood samples (13%, P < 0.001). These data suggest that LOI in tumor and normal tissue identifies most colorectal cancer patients with microsatellite instability in their tumors, and that LOI may identify an important subset of the population with cancer or at risk of developing cancer.

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Figure 1: Strategy for quantitative analysis of IGF2 imprinting in colon cancer.
Figure 2: Genomic imprinting in colorectal cancer, matched normal mucosa, and mucosa of control patients.
Figure 3: Link between LOI in colorectal cancer, LOI in matched normal mucosa, and microsatellite instability in cancer.
Figure 4: Analysis of promoter-specific imprinting in colon cancer patients.
Figure 5: Loss of imprinting in blood, colonic mucosa, and tumor of colon cancer patients.

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Acknowledgements

We thank J. Barletta, R. Robinson and K. Romans for technical assistance; P. Kwiterovich for blood samples; M. Lee, J. Nathans, T. Kelly, C. Dang, and B. Chernow for discussions; and P. Rusche for manuscript preparation. This work was supported by NIH grants CA65145 (A.P.F) and CA62924 (S.R.H.).

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Correspondence to Andrew P. Feinberg.

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Cui, H., Horon, I., Ohlsson, R. et al. Loss of imprinting in normal tissue of colorectal cancer patients with microsatellite instability. Nat Med 4, 1276–1280 (1998). https://doi.org/10.1038/3260

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