Comprehensive DNA methylation and extensive mutation analyses reveal an association between the CpG island methylator phenotype and oncogenic mutations in gastric cancers

Jeong Goo Kim; Hideyuki Takeshima; Tohru Niwa; Emil Rehnberg; Yasuyuki Shigematsu; Yukie Yoda; Satoshi Yamashita; Ryoji Kushima; Takao Maekita; Masao Ichinose; Hitoshi Katai; Won Sang Park; Young Seon Hong; Cho Hyun Park; Toshikazu Ushijima

doi:10.1016/j.canlet.2012.11.022

Comprehensive DNA methylation and extensive mutation analyses reveal an association between the CpG island methylator phenotype and oncogenic mutations in gastric cancers

Jeong Goo Kim, Hideyuki Takeshima, Tohru Niwa, Emil Rehnberg, Yasuyuki Shigematsu, Yukie Yoda, Satoshi Yamashita, Ryoji Kushima, Takao Maekita, Masao Ichinose, Hitoshi Katai, Won Sang Park, Young Seon Hong, Cho Hyun Park, Toshikazu Ushijima

Department of Pathology

Research output: Contribution to journal › Article › peer-review

55 Scopus citations

Abstract

Recent development of personal sequencers for extensive mutation analysis and bead array technology for comprehensive DNA methylation analysis have made it possible to obtain integrated pictures of genetic and epigenetic alterations on the same set of cancer samples. Here, we aimed to establish such pictures of gastric cancers (GCs). Comprehensive methylation analysis of 30 GCs revealed that the number of aberrantly methylated genes was highly variable among individual GCs. Extensive mutation analysis of 55 known cancer-related genes revealed that 19 of the 30 GCs had 24 somatic mutations of eight different genes (. CDH1, . CTNNB1, . ERBB2, . KRAS, . MLH1, . PIK3CA, . SMARCB1, and . TP53). Integration of information on the genetic and epigenetic alterations revealed that the GCs with the CpG island methylator phenotype (CIMP) tended to have mutations of oncogenes, . CTNNB1, . ERBB2, . KRAS, and . PIK3CA. This is one of the first studies in which both genetic and epigenetic alterations were extensively analyzed in the same set of samples. It was also demonstrated for the first time in GCs that the CIMP was associated with oncogene mutations.

Original language	English
Pages (from-to)	33-40
Number of pages	8
Journal	Cancer Letters
Volume	330
Issue number	1
DOIs	https://doi.org/10.1016/j.canlet.2012.11.022
State	Published - 1 Mar 2013

Bibliographical note

Funding Information:
This work was supported by Grants-in-Aid for the Third-Term Comprehensive Cancer Control Strategy from the Ministry of Health, Labour and Welfare, Japan, and by the A3 Foresight Program from the Japan Society for the Promotion of Science.

Keywords

Aberrant DNA methylation
CIMP
Epigenetics
Gastric cancer
Mutation

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1016/j.canlet.2012.11.022

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Kim, J. G., Takeshima, H., Niwa, T., Rehnberg, E., Shigematsu, Y., Yoda, Y., Yamashita, S., Kushima, R., Maekita, T., Ichinose, M., Katai, H., Park, W. S., Hong, Y. S., Park, C. H., & Ushijima, T. (2013). Comprehensive DNA methylation and extensive mutation analyses reveal an association between the CpG island methylator phenotype and oncogenic mutations in gastric cancers. Cancer Letters, 330(1), 33-40. https://doi.org/10.1016/j.canlet.2012.11.022

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title = "Comprehensive DNA methylation and extensive mutation analyses reveal an association between the CpG island methylator phenotype and oncogenic mutations in gastric cancers",

abstract = "Recent development of personal sequencers for extensive mutation analysis and bead array technology for comprehensive DNA methylation analysis have made it possible to obtain integrated pictures of genetic and epigenetic alterations on the same set of cancer samples. Here, we aimed to establish such pictures of gastric cancers (GCs). Comprehensive methylation analysis of 30 GCs revealed that the number of aberrantly methylated genes was highly variable among individual GCs. Extensive mutation analysis of 55 known cancer-related genes revealed that 19 of the 30 GCs had 24 somatic mutations of eight different genes (. CDH1, . CTNNB1, . ERBB2, . KRAS, . MLH1, . PIK3CA, . SMARCB1, and . TP53). Integration of information on the genetic and epigenetic alterations revealed that the GCs with the CpG island methylator phenotype (CIMP) tended to have mutations of oncogenes, . CTNNB1, . ERBB2, . KRAS, and . PIK3CA. This is one of the first studies in which both genetic and epigenetic alterations were extensively analyzed in the same set of samples. It was also demonstrated for the first time in GCs that the CIMP was associated with oncogene mutations.",

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note = "Funding Information: This work was supported by Grants-in-Aid for the Third-Term Comprehensive Cancer Control Strategy from the Ministry of Health, Labour and Welfare, Japan, and by the A3 Foresight Program from the Japan Society for the Promotion of Science. ",

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Kim, JG, Takeshima, H, Niwa, T, Rehnberg, E, Shigematsu, Y, Yoda, Y, Yamashita, S, Kushima, R, Maekita, T, Ichinose, M, Katai, H, Park, WS, Hong, YS, Park, CH & Ushijima, T 2013, 'Comprehensive DNA methylation and extensive mutation analyses reveal an association between the CpG island methylator phenotype and oncogenic mutations in gastric cancers', Cancer Letters, vol. 330, no. 1, pp. 33-40. https://doi.org/10.1016/j.canlet.2012.11.022

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AU - Kim, Jeong Goo

AU - Takeshima, Hideyuki

AU - Niwa, Tohru

AU - Rehnberg, Emil

AU - Shigematsu, Yasuyuki

AU - Yoda, Yukie

AU - Yamashita, Satoshi

AU - Kushima, Ryoji

AU - Maekita, Takao

AU - Ichinose, Masao

AU - Katai, Hitoshi

AU - Park, Won Sang

AU - Hong, Young Seon

AU - Park, Cho Hyun

AU - Ushijima, Toshikazu

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N2 - Recent development of personal sequencers for extensive mutation analysis and bead array technology for comprehensive DNA methylation analysis have made it possible to obtain integrated pictures of genetic and epigenetic alterations on the same set of cancer samples. Here, we aimed to establish such pictures of gastric cancers (GCs). Comprehensive methylation analysis of 30 GCs revealed that the number of aberrantly methylated genes was highly variable among individual GCs. Extensive mutation analysis of 55 known cancer-related genes revealed that 19 of the 30 GCs had 24 somatic mutations of eight different genes (. CDH1, . CTNNB1, . ERBB2, . KRAS, . MLH1, . PIK3CA, . SMARCB1, and . TP53). Integration of information on the genetic and epigenetic alterations revealed that the GCs with the CpG island methylator phenotype (CIMP) tended to have mutations of oncogenes, . CTNNB1, . ERBB2, . KRAS, and . PIK3CA. This is one of the first studies in which both genetic and epigenetic alterations were extensively analyzed in the same set of samples. It was also demonstrated for the first time in GCs that the CIMP was associated with oncogene mutations.

AB - Recent development of personal sequencers for extensive mutation analysis and bead array technology for comprehensive DNA methylation analysis have made it possible to obtain integrated pictures of genetic and epigenetic alterations on the same set of cancer samples. Here, we aimed to establish such pictures of gastric cancers (GCs). Comprehensive methylation analysis of 30 GCs revealed that the number of aberrantly methylated genes was highly variable among individual GCs. Extensive mutation analysis of 55 known cancer-related genes revealed that 19 of the 30 GCs had 24 somatic mutations of eight different genes (. CDH1, . CTNNB1, . ERBB2, . KRAS, . MLH1, . PIK3CA, . SMARCB1, and . TP53). Integration of information on the genetic and epigenetic alterations revealed that the GCs with the CpG island methylator phenotype (CIMP) tended to have mutations of oncogenes, . CTNNB1, . ERBB2, . KRAS, and . PIK3CA. This is one of the first studies in which both genetic and epigenetic alterations were extensively analyzed in the same set of samples. It was also demonstrated for the first time in GCs that the CIMP was associated with oncogene mutations.

KW - Aberrant DNA methylation

KW - CIMP

KW - Epigenetics

KW - Gastric cancer

KW - Mutation

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JF - Cancer Letters

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Comprehensive DNA methylation and extensive mutation analyses reveal an association between the CpG island methylator phenotype and oncogenic mutations in gastric cancers

Abstract

Bibliographical note

Keywords

UN SDGs

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