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

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Abstract

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.

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Acknowledgments

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).

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The authors declare that they have no conflict of interest.

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Authors and Affiliations

  1. Department of Pathology, National Cancer Center, Goyang, Gyeonggi-do, South Korea

    Seog-Yun Park & Myeong Cherl Kook

  2. Department of General Surgery, National Cancer Center, Goyang, Gyeonggi-do, South Korea

    Young Woo Kim

  3. Laboratory of Epigenetics, Cancer Research Institute, Seoul National University College of Medicine, Seoul, South Korea

    Nam-Yun Cho & Gyeong Hoon Kang

  4. Department of Internal Medicine, Seoul National University College of Medicine, Seoul, South Korea

    Tae-You Kim

  5. Department of Pathology, 2nd Stage Brain Korea Project and Seoul National University College of Medicine, Seoul, South Korea

    Gyeong Hoon Kang

  6. Department of Pathology, Seoul National University College of Medicine, 28 Yongon-dong, Chongno-gu, Seoul, 110-744, South Korea

    Gyeong Hoon Kang

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  1. Seog-Yun Park
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  2. Myeong Cherl Kook
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  3. Young Woo Kim
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  4. Nam-Yun Cho
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Correspondence to Gyeong Hoon Kang.

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Suppl. Fig. 1

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

High resolution image file (TIFF 839 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)

High resolution image file (TIFF 838 KB)

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Park, SY., Kook, M.C., Kim, Y.W. et al. Mixed-type gastric cancer and its association with high-frequency CpG island hypermethylation. Virchows Arch 456, 625–633 (2010). https://doi.org/10.1007/s00428-010-0916-6

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  • DOI: https://doi.org/10.1007/s00428-010-0916-6

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