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

研究成果: 雜誌貢獻文章

2 引文 (Scopus)

摘要

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.
原文英語
頁(從 - 到)578-585
頁數8
期刊Annals of Surgical Oncology
24
發行號2
DOIs
出版狀態已發佈 - 二月 1 2017
對外發佈Yes

指紋

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

ASJC Scopus subject areas

  • Surgery
  • Oncology

引用此文

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.

於: Annals of Surgical Oncology, 卷 24, 編號 2, 01.02.2017, p. 578-585.

研究成果: 雜誌貢獻文章

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. 於: Annals of Surgical Oncology. 2017 ; 卷 24, 編號 2. 頁 578-585.
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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.",
author = "Chen, {Hong Chang} and Huang, {Hsuan Yuan} and Chen, {Yao Li} and Lee, {Kuan Der} and Chu, {Yi Ru} and Lin, {Ping Yi} and Hsu, {Chia Chen} and Chu, {Pei Yi} and Huang, {Tim H.M.} and Hsiao, {Shu Huei} and Leu, {Yu Wei}",
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T1 - Methylation of the Tumor Suppressor Genes HIC1 and RassF1A Clusters Independently From the Methylation of Polycomb Target Genes in Colon Cancer

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

PY - 2017/2/1

Y1 - 2017/2/1

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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