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

  • Translational Research and Biomarkers
  • Published:
Annals of Surgical Oncology Aims and scope Submit manuscript

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.

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Acknowledgment

Y.W.L., S.H.H., P.Y.L., and Y.L.C. were supported by Changhua Christian Hospital, Taiwan (100-CCH-KMU-007). Y.W.L., S.H.H., and P.Y.C. were supported by NSC Taiwan (100-2320-B-194-001, 101-2320-B-194-001, and 100-2321-B-750-001). Y.W.L. and K.D.L. were supported by MoST, Taiwan (103-2314-B-182A-090). Y.W.L. and S.H.H. were supported by MoST (NSC 102-2320-B-194-003-MY3) and NHRI (NHRI-EX102-10259NI), Taiwan.

Disclosures

The authors declare that they have no commercial interests in the subject of this study.

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    Authors and Affiliations

    1. Division of Colorectal Surgery, Department of Surgery, Changhua Christian Hospital, Changhua, Taiwan

      Hong-Chang Chen MD & Hsuan-Yuan Huang MD

    2. Transplant Medicine & Surgery Research Centre, Changhua Christian Hospital, Changhua, Taiwan

      Yao-Li Chen MD & Ping-Yi Lin PhD

    3. School of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan

      Yao-Li Chen MD

    4. Department of Hematology and Oncology, Chang Gung Memorial Hospital, Chiayi, Chang Gung University College of Medicine, Taoyuan, Taiwan

      Kuan-Der Lee MD, PhD & Yi-Ru Chu MS

    5. Chang Gung Institute of Technology, Taoyuan, Taiwan

      Kuan-Der Lee MD, PhD & Yi-Ru Chu MS

    6. Department of Life Science, Human Epigenomics Center, Institute of Molecular Biology and Institute of Biomedical Science, National Chung Cheng University, Chia-Yi, Taiwan

      Yi-Ru Chu MS, Chia-Chen Hsu PhD, Shu-Huei Hsiao PhD & Yu-Wei Leu PhD

    7. Department of Pathology, Show Chwan Memorial Hospital, Changhua, Taiwan

      Pei-Yi Chu MD, PhD

    8. Department of Molecular Medicine and Institute of Biotechnology, School of Medicine, Cancer Therapy and Research Center, The University of Texas Health Science Center at San Antonio, San Antonio, TX, USA

      Tim H.-M. Huang PhD

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    Hong-Chang Chen and Hsuan-Yuan Huang have contributed equally to this paper.

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    Chen, HC., Huang, HY., Chen, YL. et al. Methylation of the Tumor Suppressor Genes HIC1 and RassF1A Clusters Independently From the Methylation of Polycomb Target Genes in Colon Cancer. Ann Surg Oncol 24, 578–585 (2017). https://doi.org/10.1245/s10434-015-5024-z

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    • DOI: https://doi.org/10.1245/s10434-015-5024-z

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