DNA hypermethylation status of multiple genes in soft tissue sarcomas

Ken Ichi Kawaguchi, Yoshinao Oda, Tsuyoshi Saito, Hidetaka Yamamoto, Tomonari Takahira, Chikashi Kobayashi, Sadafumi Tamiya, Naomi Tateishi, Yukihide Iwamoto, Masazumi Tsuneyoshi

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Abstract

The aberrant methylation of promoter CpG islands is known to be a major inactivation mechanism of tumor-related genes. To determine the clinicopathological significance of gene promoter methylation in soft tissue sarcomas, we examined the promoter methylation status of 10 tumor-related genes in 65 soft tissue sarcomas and 19 adjacent non-neoplastic tissues by methylation-specific PCR. The methylation frequencies of tumor-related genes tested in soft tissue sarcomas were 17 (26%) for RASSF1A, 11 (17%) for DAP kinase, 10 (15%) for MGMT, nine (14%) for GSTP1, eight (12%) for PTEN, six (9%) for p16 and hMLH1, five (8%) for hMSH2, two (3%) for p14, and one (2%) for RB. Promoter methylation of these genes was not recognized in non-neoplastic tissues. All those cases of soft tissue sarcoma that had MGMT methylation, with the exception of one case of malignant peripheral nerve sheath tumor, showed large tumor size (≥10 cm) or recurrence. Moreover, eight of 10 cases with MGMT methylation revealed high American Joint Committee on Cancer stage. Seven of 10 cases (70%) with MGMT methylation showed a loss of MGMT expression by immunohistochemistry. In addition, MGMT methylation status had a statistically significant correlation with a loss of MGMT expression (P = 0.014). In conclusion, although methylation of tumor-related genes was a relatively rare event in soft tissue sarcomas, methylation was tumor-specific. Of 10 tumor-related genes, cases with MGMT methylation had a tendency to be aggressive behavior. Moreover, MGMT methylation was closely associated with a loss of MGMT expression. Although our findings need to be extending to a large series, promoter methylation of tumor-related genes is likely to have an association with the pathogenesis of soft tissue sarcomas. Furthermore, MGMT methylation may be associated with tumor aggressiveness and the inactivation of MGMT gene.

Original languageEnglish
Pages (from-to)106-114
Number of pages9
JournalModern Pathology
Volume19
Issue number1
DOIs
Publication statusPublished - Jan 1 2006

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Sarcoma
Methylation
DNA
Genes
Neoplasms
Death-Associated Protein Kinases
CpG Islands
Neurilemmoma
Gene Silencing
Carcinogens

All Science Journal Classification (ASJC) codes

  • Pathology and Forensic Medicine

Cite this

DNA hypermethylation status of multiple genes in soft tissue sarcomas. / Kawaguchi, Ken Ichi; Oda, Yoshinao; Saito, Tsuyoshi; Yamamoto, Hidetaka; Takahira, Tomonari; Kobayashi, Chikashi; Tamiya, Sadafumi; Tateishi, Naomi; Iwamoto, Yukihide; Tsuneyoshi, Masazumi.

In: Modern Pathology, Vol. 19, No. 1, 01.01.2006, p. 106-114.

Research output: Contribution to journalArticle

Kawaguchi, KI, Oda, Y, Saito, T, Yamamoto, H, Takahira, T, Kobayashi, C, Tamiya, S, Tateishi, N, Iwamoto, Y & Tsuneyoshi, M 2006, 'DNA hypermethylation status of multiple genes in soft tissue sarcomas', Modern Pathology, vol. 19, no. 1, pp. 106-114. https://doi.org/10.1038/modpathol.3800502
Kawaguchi, Ken Ichi ; Oda, Yoshinao ; Saito, Tsuyoshi ; Yamamoto, Hidetaka ; Takahira, Tomonari ; Kobayashi, Chikashi ; Tamiya, Sadafumi ; Tateishi, Naomi ; Iwamoto, Yukihide ; Tsuneyoshi, Masazumi. / DNA hypermethylation status of multiple genes in soft tissue sarcomas. In: Modern Pathology. 2006 ; Vol. 19, No. 1. pp. 106-114.
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abstract = "The aberrant methylation of promoter CpG islands is known to be a major inactivation mechanism of tumor-related genes. To determine the clinicopathological significance of gene promoter methylation in soft tissue sarcomas, we examined the promoter methylation status of 10 tumor-related genes in 65 soft tissue sarcomas and 19 adjacent non-neoplastic tissues by methylation-specific PCR. The methylation frequencies of tumor-related genes tested in soft tissue sarcomas were 17 (26{\%}) for RASSF1A, 11 (17{\%}) for DAP kinase, 10 (15{\%}) for MGMT, nine (14{\%}) for GSTP1, eight (12{\%}) for PTEN, six (9{\%}) for p16 and hMLH1, five (8{\%}) for hMSH2, two (3{\%}) for p14, and one (2{\%}) for RB. Promoter methylation of these genes was not recognized in non-neoplastic tissues. All those cases of soft tissue sarcoma that had MGMT methylation, with the exception of one case of malignant peripheral nerve sheath tumor, showed large tumor size (≥10 cm) or recurrence. Moreover, eight of 10 cases with MGMT methylation revealed high American Joint Committee on Cancer stage. Seven of 10 cases (70{\%}) with MGMT methylation showed a loss of MGMT expression by immunohistochemistry. In addition, MGMT methylation status had a statistically significant correlation with a loss of MGMT expression (P = 0.014). In conclusion, although methylation of tumor-related genes was a relatively rare event in soft tissue sarcomas, methylation was tumor-specific. Of 10 tumor-related genes, cases with MGMT methylation had a tendency to be aggressive behavior. Moreover, MGMT methylation was closely associated with a loss of MGMT expression. Although our findings need to be extending to a large series, promoter methylation of tumor-related genes is likely to have an association with the pathogenesis of soft tissue sarcomas. Furthermore, MGMT methylation may be associated with tumor aggressiveness and the inactivation of MGMT gene.",
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