Different methylation profiles between intestinal and diffuse sporadic gastric carcinogenesis

Misuk Yang, Hyunsoo Kim, Meeyon Cho

Research output: Contribution to journalArticle

10 Citations (Scopus)

Abstract

Objective: Gastric cancer (GC) is histologically classified into intestinal type and diffuse type, and diffuse type cancer can be further subdivided into poorly differentiated carcinoma (PDC) and signet ring cell carcinoma (SRCC). Recent evidence suggests that early SRCC is an initial, differentiated form of diffuse GC that may evolve into PDC. This study aimed at identifying the molecular features of epigenetic methylation changes in histologic differentiation status of GC. Methods: Included in this study are 149 samples of paraffin-embedded tissues and 115 fresh endoscopically biopsied tissues. Multiple paraffin tissues involving normal (n=. 22), dysplasias (GDs, n=. 39), differentiated cancers (DCs, n=. 35), PDCs (n=. 33) and SRCCs (n=. 20) were included as an experimental group. For the validation group, endoscopically biopsied tissues of DCs (n=. 50), PDCs (n=. 31), and SRCs (n=. 34) were analyzed. DNAs, isolated from each group were analyzed to determine the methylation status of 6 genes (GDNF, RORA, MINT25, KLF7, CDH1, LINE-1) using pyrosequencing. Results: LINE-1 was hypomethylated in GCs compared to normal and GD. GDNF, RORA and MINT25 were more hypermethylated in intestinal type GCs than those of diffuse type GCs, whereas CDH1 showed opposite patterns of methylation. Among diffuse type GCs, SRCCs showed lower level of methylation for GDNF, RORA, MINT25 and KLF7, and higher level for CDH1 compared to PDCs. Conclusions: In conclusion, intestinal type of GCs shows different epigenetic methylation profiles compared to the diffuse one. Moreover, SRCCs have different methylation profiles compared with PDCs, suggesting a unique molecular pathway in the gastric carcinogenesis.

Original languageEnglish
Pages (from-to)613-620
Number of pages8
JournalClinics and Research in Hepatology and Gastroenterology
Volume38
Issue number5
DOIs
Publication statusPublished - 2014 Jan 1

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Methylation
Stomach
Carcinogenesis
Glial Cell Line-Derived Neurotrophic Factor
Signet Ring Cell Carcinoma
Stomach Neoplasms
Epigenomics
Paraffin
Carcinoma
Neoplasms
DNA
Genes

All Science Journal Classification (ASJC) codes

  • Gastroenterology
  • Medicine(all)

Cite this

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title = "Different methylation profiles between intestinal and diffuse sporadic gastric carcinogenesis",
abstract = "Objective: Gastric cancer (GC) is histologically classified into intestinal type and diffuse type, and diffuse type cancer can be further subdivided into poorly differentiated carcinoma (PDC) and signet ring cell carcinoma (SRCC). Recent evidence suggests that early SRCC is an initial, differentiated form of diffuse GC that may evolve into PDC. This study aimed at identifying the molecular features of epigenetic methylation changes in histologic differentiation status of GC. Methods: Included in this study are 149 samples of paraffin-embedded tissues and 115 fresh endoscopically biopsied tissues. Multiple paraffin tissues involving normal (n=. 22), dysplasias (GDs, n=. 39), differentiated cancers (DCs, n=. 35), PDCs (n=. 33) and SRCCs (n=. 20) were included as an experimental group. For the validation group, endoscopically biopsied tissues of DCs (n=. 50), PDCs (n=. 31), and SRCs (n=. 34) were analyzed. DNAs, isolated from each group were analyzed to determine the methylation status of 6 genes (GDNF, RORA, MINT25, KLF7, CDH1, LINE-1) using pyrosequencing. Results: LINE-1 was hypomethylated in GCs compared to normal and GD. GDNF, RORA and MINT25 were more hypermethylated in intestinal type GCs than those of diffuse type GCs, whereas CDH1 showed opposite patterns of methylation. Among diffuse type GCs, SRCCs showed lower level of methylation for GDNF, RORA, MINT25 and KLF7, and higher level for CDH1 compared to PDCs. Conclusions: In conclusion, intestinal type of GCs shows different epigenetic methylation profiles compared to the diffuse one. Moreover, SRCCs have different methylation profiles compared with PDCs, suggesting a unique molecular pathway in the gastric carcinogenesis.",
author = "Misuk Yang and Hyunsoo Kim and Meeyon Cho",
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T1 - Different methylation profiles between intestinal and diffuse sporadic gastric carcinogenesis

AU - Yang, Misuk

AU - Kim, Hyunsoo

AU - Cho, Meeyon

PY - 2014/1/1

Y1 - 2014/1/1

N2 - Objective: Gastric cancer (GC) is histologically classified into intestinal type and diffuse type, and diffuse type cancer can be further subdivided into poorly differentiated carcinoma (PDC) and signet ring cell carcinoma (SRCC). Recent evidence suggests that early SRCC is an initial, differentiated form of diffuse GC that may evolve into PDC. This study aimed at identifying the molecular features of epigenetic methylation changes in histologic differentiation status of GC. Methods: Included in this study are 149 samples of paraffin-embedded tissues and 115 fresh endoscopically biopsied tissues. Multiple paraffin tissues involving normal (n=. 22), dysplasias (GDs, n=. 39), differentiated cancers (DCs, n=. 35), PDCs (n=. 33) and SRCCs (n=. 20) were included as an experimental group. For the validation group, endoscopically biopsied tissues of DCs (n=. 50), PDCs (n=. 31), and SRCs (n=. 34) were analyzed. DNAs, isolated from each group were analyzed to determine the methylation status of 6 genes (GDNF, RORA, MINT25, KLF7, CDH1, LINE-1) using pyrosequencing. Results: LINE-1 was hypomethylated in GCs compared to normal and GD. GDNF, RORA and MINT25 were more hypermethylated in intestinal type GCs than those of diffuse type GCs, whereas CDH1 showed opposite patterns of methylation. Among diffuse type GCs, SRCCs showed lower level of methylation for GDNF, RORA, MINT25 and KLF7, and higher level for CDH1 compared to PDCs. Conclusions: In conclusion, intestinal type of GCs shows different epigenetic methylation profiles compared to the diffuse one. Moreover, SRCCs have different methylation profiles compared with PDCs, suggesting a unique molecular pathway in the gastric carcinogenesis.

AB - Objective: Gastric cancer (GC) is histologically classified into intestinal type and diffuse type, and diffuse type cancer can be further subdivided into poorly differentiated carcinoma (PDC) and signet ring cell carcinoma (SRCC). Recent evidence suggests that early SRCC is an initial, differentiated form of diffuse GC that may evolve into PDC. This study aimed at identifying the molecular features of epigenetic methylation changes in histologic differentiation status of GC. Methods: Included in this study are 149 samples of paraffin-embedded tissues and 115 fresh endoscopically biopsied tissues. Multiple paraffin tissues involving normal (n=. 22), dysplasias (GDs, n=. 39), differentiated cancers (DCs, n=. 35), PDCs (n=. 33) and SRCCs (n=. 20) were included as an experimental group. For the validation group, endoscopically biopsied tissues of DCs (n=. 50), PDCs (n=. 31), and SRCs (n=. 34) were analyzed. DNAs, isolated from each group were analyzed to determine the methylation status of 6 genes (GDNF, RORA, MINT25, KLF7, CDH1, LINE-1) using pyrosequencing. Results: LINE-1 was hypomethylated in GCs compared to normal and GD. GDNF, RORA and MINT25 were more hypermethylated in intestinal type GCs than those of diffuse type GCs, whereas CDH1 showed opposite patterns of methylation. Among diffuse type GCs, SRCCs showed lower level of methylation for GDNF, RORA, MINT25 and KLF7, and higher level for CDH1 compared to PDCs. Conclusions: In conclusion, intestinal type of GCs shows different epigenetic methylation profiles compared to the diffuse one. Moreover, SRCCs have different methylation profiles compared with PDCs, suggesting a unique molecular pathway in the gastric carcinogenesis.

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