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

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

Research output: Contribution to journalArticle

2 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)578-585
Number of pages8
JournalAnnals of Surgical Oncology
Volume24
Issue number2
DOIs
Publication statusPublished - Feb 1 2017
Externally publishedYes

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Tumor Suppressor Genes
Colonic Neoplasms
Methylation
Genes
Chromatin
Neoplasms
Neoplastic Stem Cells
DNA Methylation
Liver Neoplasms
Epigenomics

ASJC Scopus subject areas

  • Surgery
  • Oncology

Cite this

Methylation of the Tumor Suppressor Genes HIC1 and RassF1A Clusters Independently From the Methylation of Polycomb Target Genes in Colon Cancer. / Chen, Hong Chang; Huang, Hsuan Yuan; Chen, Yao Li; Lee, Kuan Der; Chu, Yi Ru; Lin, Ping Yi; Hsu, Chia Chen; Chu, Pei Yi; Huang, Tim H.M.; Hsiao, Shu Huei; Leu, Yu Wei.

In: Annals of Surgical Oncology, Vol. 24, No. 2, 01.02.2017, p. 578-585.

Research output: Contribution to journalArticle

Chen, Hong Chang ; Huang, Hsuan Yuan ; Chen, Yao Li ; Lee, Kuan Der ; Chu, Yi Ru ; Lin, Ping Yi ; Hsu, Chia Chen ; Chu, Pei Yi ; Huang, Tim H.M. ; Hsiao, Shu Huei ; Leu, Yu Wei. / Methylation of the Tumor Suppressor Genes HIC1 and RassF1A Clusters Independently From the Methylation of Polycomb Target Genes in Colon Cancer. In: Annals of Surgical Oncology. 2017 ; Vol. 24, No. 2. pp. 578-585.
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AU - Chen, Hong Chang

AU - Huang, Hsuan Yuan

AU - Chen, Yao Li

AU - Lee, Kuan Der

AU - Chu, Yi Ru

AU - Lin, Ping Yi

AU - Hsu, Chia Chen

AU - Chu, Pei Yi

AU - Huang, Tim H.M.

AU - Hsiao, Shu Huei

AU - Leu, Yu Wei

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N2 - 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.

AB - 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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