Virchows Archiv

, Volume 456, Issue 6, pp 625–633 | Cite as

Mixed-type gastric cancer and its association with high-frequency CpG island hypermethylation

  • Seog-Yun Park
  • Myeong Cherl Kook
  • Young Woo Kim
  • Nam-Yun Cho
  • Tae-You Kim
  • Gyeong Hoon KangEmail author
Original Article


Gastric carcinoma (GC) is one of the human cancers in which promoter CpG island hypermethylation is frequently found. We used the MethyLight assay to evaluate the methylation status of 16 CpG island loci that are hypermethylated in GC. We analyzed the relationship between CpG island hypermethylation of these 16 genes and the clinicopathological features in 191 advanced GCs. A significant difference was observed between the number of methylated genes in Epstein-Barr virus (EBV)-negative and microsatellite instability (MSI)-negative GCs of different histological types (Lauren classification; P < 0.01). We found that mixed-type (MT) carcinomas, which have both diffuse-type (DT) and intestinal-type (IT) components, had more methylated genes (10.6) than either DT carcinomas (7.6 methylated genes) or IT carcinomas (6.7 methylated genes) (P < 0.001). This trend was also observed when EBV-positive or MSI-positive GCs were excluded from the analysis (9.2, 6.9, and 4.8; P < 0.001). When the IT and DT components were dissected from MT carcinomas and the methylation of these 16 genes was evaluated, both components had a number of methylated genes similar to MT carcinomas, (10.2 and 9.7, respectively), which was significantly higher than was found in IT and DT carcinomas (P < 0.05). These findings indicate that MT carcinoma is distinct from IT and DT carcinomas in its enhanced CpG island hypermethylation status and implicate the enhanced promoter CpG island hypermethylation in the histogenesis of MT carcinoma.


CpG island DNA methylation Gastric cancer Histologic type 



This study was supported by a grant of the Korea Healthcare Technology R&D Project, Ministry for Health, Welfare & Family Affairs, Republic of Korea (A090126).


The authors declare that they have no conflict of interest.

Supplementary material

428_2010_916_Fig1_ESM.gif (32 kb)
Suppl. Fig. 1

Methylation frequencies of 16 individual genes in gastric cancer samples (n = 191). (JPEG 31.6 KB)

428_2010_916_Fig1_ESM.tif (839 kb)
High resolution image file (TIFF 839 KB)
428_2010_916_Fig2_ESM.gif (30 kb)
Suppl. Fig. 2

Interindividual concordance in methylation of 16 genes. To identify concordance, we compared the number of genes methylated in 15 genes (excluding the gene that was being evaluated) for the association of its methylation status with that of the other genes. ANOVA was used, and significant concordance of methylation was shown for all the genes (p< 0.01). (JPEG 29.7 KB)

428_2010_916_Fig2_ESM.tif (839 kb)
High resolution image file (TIFF 838 KB)


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Copyright information

© Springer-Verlag 2010

Authors and Affiliations

  • Seog-Yun Park
    • 1
  • Myeong Cherl Kook
    • 1
  • Young Woo Kim
    • 2
  • Nam-Yun Cho
    • 3
  • Tae-You Kim
    • 4
  • Gyeong Hoon Kang
    • 3
    • 5
    • 6
    Email author
  1. 1.Department of PathologyNational Cancer CenterGoyangSouth Korea
  2. 2.Department of General SurgeryNational Cancer CenterGoyangSouth Korea
  3. 3.Laboratory of EpigeneticsCancer Research Institute, Seoul National University College of MedicineSeoulSouth Korea
  4. 4.Department of Internal MedicineSeoul National University College of MedicineSeoulSouth Korea
  5. 5.Department of Pathology2nd Stage Brain Korea Project and Seoul National University College of MedicineSeoulSouth Korea
  6. 6.Department of PathologySeoul National University College of MedicineSeoulSouth Korea

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