DNA methylation status of a distinctively different subset of genes is associated with each histologic Lauren classification subtype in early gastric carcinogenesis

Yosep Chong, Khalilullah Mia-jan, Hoon Ryu, Jamshid Abdul-Ghafar, Jijgee Munkhdelger, Sayamaa Lkhagvadorj, So Young Jung, Mira Lee, Sun Young Ji, Eunhee Choi, Mee Yon Cho

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Abstract

DNA methylation change is known to play a crucial role in early gastric carcinogenesis. The present study aimed to identify and validate the correlation between differentially methylated regions (DMRs) and the subtypes of early gastric cancers (EGCs). Illumina Infinium methylation assay (IIMA; 450K BeadChip kit) was performed on fresh tumor and non- tumor tissues of 12 EGCs to screen the methylation status of 450,000 CpG sites. To evaluate the significance of DNA methylation in each histologic subtype, pyrosequencing assay (PA) was performed on 38 EGCs (18 intestinal-, 12 mixed- and 8 diffuse-type) using 12 genes selected from the screening. Between tumors of the intestinal-type (n=6), and diffuse- (n=4) plus mixed-types (n=2), 169 regions showed significant differences (intensity >3,000, Δβ >0.2) in IIMA. Hierarchical clustering using the 169 DMRs revealed distinct separation between the two groups. In PA using 12 selected genes from the IIMA results, the aberrant methylation statuses of DVL2 (p=0.0186) and ETS1 (p=0.0222) were significantly related to diffuse- and mixed-types rather than the intestinal-type, while C19orf35 (p=0.019) and CNRIP1 (p=0.0473) were related to the diffuse- type rather than intestinal- type, and GAL3ST2 (p=0.0158) and ITGA3 (p=0.0273) were related to the mixed-type rather than the other two types. The methylation of other genes, CLIP4, XKR6, CCDC57, MAML3 and SDC2, was related with age, tumor location, or Helicobacter infection rather than the histologic subtype. Aberrant DNA methylation of certain genes may be independently involved in each histologic subtype of EGC. Furthermore, mixed-type EGCs may be a distinctive histologic subtype based on the different subset of DMRs compared to those of other subtypes.

Original languageEnglish
Pages (from-to)2535-2544
Number of pages10
JournalOncology Reports
Volume31
Issue number6
DOIs
Publication statusPublished - 2014 Jun

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DNA Methylation
Stomach Neoplasms
Stomach
Carcinogenesis
Methylation
Genes
Neoplasms
Helicobacter Infections
Cluster Analysis

All Science Journal Classification (ASJC) codes

  • Oncology
  • Cancer Research

Cite this

Chong, Yosep ; Mia-jan, Khalilullah ; Ryu, Hoon ; Abdul-Ghafar, Jamshid ; Munkhdelger, Jijgee ; Lkhagvadorj, Sayamaa ; Jung, So Young ; Lee, Mira ; Ji, Sun Young ; Choi, Eunhee ; Cho, Mee Yon. / DNA methylation status of a distinctively different subset of genes is associated with each histologic Lauren classification subtype in early gastric carcinogenesis. In: Oncology Reports. 2014 ; Vol. 31, No. 6. pp. 2535-2544.
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abstract = "DNA methylation change is known to play a crucial role in early gastric carcinogenesis. The present study aimed to identify and validate the correlation between differentially methylated regions (DMRs) and the subtypes of early gastric cancers (EGCs). Illumina Infinium methylation assay (IIMA; 450K BeadChip kit) was performed on fresh tumor and non- tumor tissues of 12 EGCs to screen the methylation status of 450,000 CpG sites. To evaluate the significance of DNA methylation in each histologic subtype, pyrosequencing assay (PA) was performed on 38 EGCs (18 intestinal-, 12 mixed- and 8 diffuse-type) using 12 genes selected from the screening. Between tumors of the intestinal-type (n=6), and diffuse- (n=4) plus mixed-types (n=2), 169 regions showed significant differences (intensity >3,000, Δβ >0.2) in IIMA. Hierarchical clustering using the 169 DMRs revealed distinct separation between the two groups. In PA using 12 selected genes from the IIMA results, the aberrant methylation statuses of DVL2 (p=0.0186) and ETS1 (p=0.0222) were significantly related to diffuse- and mixed-types rather than the intestinal-type, while C19orf35 (p=0.019) and CNRIP1 (p=0.0473) were related to the diffuse- type rather than intestinal- type, and GAL3ST2 (p=0.0158) and ITGA3 (p=0.0273) were related to the mixed-type rather than the other two types. The methylation of other genes, CLIP4, XKR6, CCDC57, MAML3 and SDC2, was related with age, tumor location, or Helicobacter infection rather than the histologic subtype. Aberrant DNA methylation of certain genes may be independently involved in each histologic subtype of EGC. Furthermore, mixed-type EGCs may be a distinctive histologic subtype based on the different subset of DMRs compared to those of other subtypes.",
author = "Yosep Chong and Khalilullah Mia-jan and Hoon Ryu and Jamshid Abdul-Ghafar and Jijgee Munkhdelger and Sayamaa Lkhagvadorj and Jung, {So Young} and Mira Lee and Ji, {Sun Young} and Eunhee Choi and Cho, {Mee Yon}",
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Chong, Y, Mia-jan, K, Ryu, H, Abdul-Ghafar, J, Munkhdelger, J, Lkhagvadorj, S, Jung, SY, Lee, M, Ji, SY, Choi, E & Cho, MY 2014, 'DNA methylation status of a distinctively different subset of genes is associated with each histologic Lauren classification subtype in early gastric carcinogenesis', Oncology Reports, vol. 31, no. 6, pp. 2535-2544. https://doi.org/10.3892/or.2014.3133

DNA methylation status of a distinctively different subset of genes is associated with each histologic Lauren classification subtype in early gastric carcinogenesis. / Chong, Yosep; Mia-jan, Khalilullah; Ryu, Hoon; Abdul-Ghafar, Jamshid; Munkhdelger, Jijgee; Lkhagvadorj, Sayamaa; Jung, So Young; Lee, Mira; Ji, Sun Young; Choi, Eunhee; Cho, Mee Yon.

In: Oncology Reports, Vol. 31, No. 6, 06.2014, p. 2535-2544.

Research output: Contribution to journalArticle

TY - JOUR

T1 - DNA methylation status of a distinctively different subset of genes is associated with each histologic Lauren classification subtype in early gastric carcinogenesis

AU - Chong, Yosep

AU - Mia-jan, Khalilullah

AU - Ryu, Hoon

AU - Abdul-Ghafar, Jamshid

AU - Munkhdelger, Jijgee

AU - Lkhagvadorj, Sayamaa

AU - Jung, So Young

AU - Lee, Mira

AU - Ji, Sun Young

AU - Choi, Eunhee

AU - Cho, Mee Yon

PY - 2014/6

Y1 - 2014/6

N2 - DNA methylation change is known to play a crucial role in early gastric carcinogenesis. The present study aimed to identify and validate the correlation between differentially methylated regions (DMRs) and the subtypes of early gastric cancers (EGCs). Illumina Infinium methylation assay (IIMA; 450K BeadChip kit) was performed on fresh tumor and non- tumor tissues of 12 EGCs to screen the methylation status of 450,000 CpG sites. To evaluate the significance of DNA methylation in each histologic subtype, pyrosequencing assay (PA) was performed on 38 EGCs (18 intestinal-, 12 mixed- and 8 diffuse-type) using 12 genes selected from the screening. Between tumors of the intestinal-type (n=6), and diffuse- (n=4) plus mixed-types (n=2), 169 regions showed significant differences (intensity >3,000, Δβ >0.2) in IIMA. Hierarchical clustering using the 169 DMRs revealed distinct separation between the two groups. In PA using 12 selected genes from the IIMA results, the aberrant methylation statuses of DVL2 (p=0.0186) and ETS1 (p=0.0222) were significantly related to diffuse- and mixed-types rather than the intestinal-type, while C19orf35 (p=0.019) and CNRIP1 (p=0.0473) were related to the diffuse- type rather than intestinal- type, and GAL3ST2 (p=0.0158) and ITGA3 (p=0.0273) were related to the mixed-type rather than the other two types. The methylation of other genes, CLIP4, XKR6, CCDC57, MAML3 and SDC2, was related with age, tumor location, or Helicobacter infection rather than the histologic subtype. Aberrant DNA methylation of certain genes may be independently involved in each histologic subtype of EGC. Furthermore, mixed-type EGCs may be a distinctive histologic subtype based on the different subset of DMRs compared to those of other subtypes.

AB - DNA methylation change is known to play a crucial role in early gastric carcinogenesis. The present study aimed to identify and validate the correlation between differentially methylated regions (DMRs) and the subtypes of early gastric cancers (EGCs). Illumina Infinium methylation assay (IIMA; 450K BeadChip kit) was performed on fresh tumor and non- tumor tissues of 12 EGCs to screen the methylation status of 450,000 CpG sites. To evaluate the significance of DNA methylation in each histologic subtype, pyrosequencing assay (PA) was performed on 38 EGCs (18 intestinal-, 12 mixed- and 8 diffuse-type) using 12 genes selected from the screening. Between tumors of the intestinal-type (n=6), and diffuse- (n=4) plus mixed-types (n=2), 169 regions showed significant differences (intensity >3,000, Δβ >0.2) in IIMA. Hierarchical clustering using the 169 DMRs revealed distinct separation between the two groups. In PA using 12 selected genes from the IIMA results, the aberrant methylation statuses of DVL2 (p=0.0186) and ETS1 (p=0.0222) were significantly related to diffuse- and mixed-types rather than the intestinal-type, while C19orf35 (p=0.019) and CNRIP1 (p=0.0473) were related to the diffuse- type rather than intestinal- type, and GAL3ST2 (p=0.0158) and ITGA3 (p=0.0273) were related to the mixed-type rather than the other two types. The methylation of other genes, CLIP4, XKR6, CCDC57, MAML3 and SDC2, was related with age, tumor location, or Helicobacter infection rather than the histologic subtype. Aberrant DNA methylation of certain genes may be independently involved in each histologic subtype of EGC. Furthermore, mixed-type EGCs may be a distinctive histologic subtype based on the different subset of DMRs compared to those of other subtypes.

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