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Annals of Surgical Oncology
Published in: Annals of Surgical Oncology 2/2017

01-02-2017 | Translational Research and Biomarkers

Methylation of the Tumor Suppressor Genes HIC1 and RassF1A Clusters Independently From the Methylation of Polycomb Target Genes in Colon Cancer

Authors: Hong-Chang Chen, MD, Hsuan-Yuan Huang, MD, Yao-Li Chen, MD, Kuan-Der Lee, MD, PhD, Yi-Ru Chu, MS, Ping-Yi Lin, PhD, Chia-Chen Hsu, PhD, Pei-Yi Chu, MD, PhD, Tim H.-M. Huang, PhD, Shu-Huei Hsiao, PhD, Yu-Wei Leu, PhD

Published in: Annals of Surgical Oncology | Issue 2/2017

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Abstract

Background

Methylation changes within tumor suppressor (TS) genes or polycomb group target (PcG) genes alter cell fates. Chromatin associated with PcG targets is bivalent in stem cells, while TS genes are not normally bivalent. PcG target methylation changes have been identified in tumor stem cells, and abnormal methylation is found in TS genes in cancers. If the epigenetic states of genes influence DNA methylation, then methylation of PcG targets and TS genes may evolve differently during cancer development. More importantly, methylation changes may be part of a sequence in tumorigenesis.

Methods

Chromatin and methylation states of 4 PcG targets and 2 TS genes were determined in colon cancer cells. The methylation states were also detected in 100 pairs of colon cancer samples. Principle component analysis (PCA) was used to reveal whether TS methylation or PcG methylation was the main methylation change associated with colon cancers.

Results

Chromatin and methylation states differ in colon cancer cell lines. The methylation states within PcG targets clustered independently from the methylation states in TS genes, a finding we previously reported in liver cancers. PCA in colon cancers revealed the strongest association with methylation changes in 2 TS genes, HIC1 and RassF1A. Loss of HIC1 methylation correlated with decreased tumor migration.

Conclusions

PcG and TS methylation states cluster independently from each other. The deduced principle component correlated better with TS methylation than PcG methylation in colon cancer. Abnormal methylation changes may represent a sequential biomarker profile to identify developing colon cancer.
Appendix
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Metadata
Title
Methylation of the Tumor Suppressor Genes HIC1 and RassF1A Clusters Independently From the Methylation of Polycomb Target Genes in Colon Cancer
Authors
Hong-Chang Chen, MD
Hsuan-Yuan Huang, MD
Yao-Li Chen, MD
Kuan-Der Lee, MD, PhD
Yi-Ru Chu, MS
Ping-Yi Lin, PhD
Chia-Chen Hsu, PhD
Pei-Yi Chu, MD, PhD
Tim H.-M. Huang, PhD
Shu-Huei Hsiao, PhD
Yu-Wei Leu, PhD
Publication date
01-02-2017
Publisher
Springer International Publishing
Published in
Annals of Surgical Oncology / Issue 2/2017
Print ISSN: 1068-9265
Electronic ISSN: 1534-4681
DOI
https://doi.org/10.1245/s10434-015-5024-z

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