Methylation status of EXT1 and EXT2 promoters and two mutations of EXT2 in chondrosarcoma

Takashi Tsuchiya, Toshihisa Osanai, Akira Ogose, Gen Tamura, Tokuhiro Chano, Yasuhiko Kaneko, Akira Ishikawa, Hiroshi Orui, Takuro Wada, Tatsuru Ikeda, Masayoshi Namba, Masaharu Takigawa, Hiroyuki Kawashima, Tetsuo Hotta, Atsushi Tsuchiya, Toshihiko Ogino, Teiichi Motoyama

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Abstract

Germline mutation and functional loss of EXT1 or EXT2 are commonly found in multiple osteochondromas and predispose to the development of chondrosarcoma. Mutations of EXT1 and EXT2 have rarely been detected in sporadic secondary chondrosarcomas from osteochondroma; these frequently display loss of heterozygosity at the EXT1 and EXT2 loci, but primary chondrosarcomas typically do not. To evaluate promoter methylation (which is an epigenetic gene silencing mechanism) of EXT1 and EXT2, we performed methylation-specific polymerase chain reaction (PCR) for 20 chondrosarcoma cases (12 primary, 3 secondary to osteochondroma, 2 secondary to enchondromatosis, 2 extraskeletal ordinary, and 1 clear cell) and in five cell lines. In addition, mutation analysis of the EXT1 and EXT2 coding regions was performed using PCR-single-strand conformation polymorphism and sequencing analysis for 12 of the 20 chondrosarcoma cases (8 primary, 1 secondary to enchondromatosis, 1 secondary to osteochondroma, and 2 extraskeletal ordinary) and five cell lines. Promoter methylation of EXT1 and EXT2 was not detected in any of the cases, and both EXT1 and EXT2 were expressed in all cell lines. Two missense mutations in EXT2 (D227E and R299H) were detected among the chondrosarcoma cases. When considering tumor development in primary chondrosarcoma, we should include mutations in EXT2, along with the status of other members of the EXT gene family.

Original languageEnglish
Pages (from-to)148-155
Number of pages8
JournalCancer Genetics and Cytogenetics
Volume158
Issue number2
DOIs
Publication statusPublished - Apr 15 2005

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Chondrosarcoma
Methylation
Mutation
Osteochondroma
Enchondromatosis
Cell Line
Multiple Hereditary Exostoses
Polymerase Chain Reaction
Germ-Line Mutation
Loss of Heterozygosity
Gene Silencing
Missense Mutation
Epigenomics
Genes

ASJC Scopus subject areas

  • Cancer Research
  • Genetics
  • Molecular Biology

Cite this

Tsuchiya, T., Osanai, T., Ogose, A., Tamura, G., Chano, T., Kaneko, Y., ... Motoyama, T. (2005). Methylation status of EXT1 and EXT2 promoters and two mutations of EXT2 in chondrosarcoma. Cancer Genetics and Cytogenetics, 158(2), 148-155. https://doi.org/10.1016/j.cancergencyto.2004.08.031

Methylation status of EXT1 and EXT2 promoters and two mutations of EXT2 in chondrosarcoma. / Tsuchiya, Takashi; Osanai, Toshihisa; Ogose, Akira; Tamura, Gen; Chano, Tokuhiro; Kaneko, Yasuhiko; Ishikawa, Akira; Orui, Hiroshi; Wada, Takuro; Ikeda, Tatsuru; Namba, Masayoshi; Takigawa, Masaharu; Kawashima, Hiroyuki; Hotta, Tetsuo; Tsuchiya, Atsushi; Ogino, Toshihiko; Motoyama, Teiichi.

In: Cancer Genetics and Cytogenetics, Vol. 158, No. 2, 15.04.2005, p. 148-155.

Research output: Contribution to journalArticle

Tsuchiya, T, Osanai, T, Ogose, A, Tamura, G, Chano, T, Kaneko, Y, Ishikawa, A, Orui, H, Wada, T, Ikeda, T, Namba, M, Takigawa, M, Kawashima, H, Hotta, T, Tsuchiya, A, Ogino, T & Motoyama, T 2005, 'Methylation status of EXT1 and EXT2 promoters and two mutations of EXT2 in chondrosarcoma', Cancer Genetics and Cytogenetics, vol. 158, no. 2, pp. 148-155. https://doi.org/10.1016/j.cancergencyto.2004.08.031
Tsuchiya, Takashi ; Osanai, Toshihisa ; Ogose, Akira ; Tamura, Gen ; Chano, Tokuhiro ; Kaneko, Yasuhiko ; Ishikawa, Akira ; Orui, Hiroshi ; Wada, Takuro ; Ikeda, Tatsuru ; Namba, Masayoshi ; Takigawa, Masaharu ; Kawashima, Hiroyuki ; Hotta, Tetsuo ; Tsuchiya, Atsushi ; Ogino, Toshihiko ; Motoyama, Teiichi. / Methylation status of EXT1 and EXT2 promoters and two mutations of EXT2 in chondrosarcoma. In: Cancer Genetics and Cytogenetics. 2005 ; Vol. 158, No. 2. pp. 148-155.
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AU - Tsuchiya, Takashi

AU - Osanai, Toshihisa

AU - Ogose, Akira

AU - Tamura, Gen

AU - Chano, Tokuhiro

AU - Kaneko, Yasuhiko

AU - Ishikawa, Akira

AU - Orui, Hiroshi

AU - Wada, Takuro

AU - Ikeda, Tatsuru

AU - Namba, Masayoshi

AU - Takigawa, Masaharu

AU - Kawashima, Hiroyuki

AU - Hotta, Tetsuo

AU - Tsuchiya, Atsushi

AU - Ogino, Toshihiko

AU - Motoyama, Teiichi

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N2 - Germline mutation and functional loss of EXT1 or EXT2 are commonly found in multiple osteochondromas and predispose to the development of chondrosarcoma. Mutations of EXT1 and EXT2 have rarely been detected in sporadic secondary chondrosarcomas from osteochondroma; these frequently display loss of heterozygosity at the EXT1 and EXT2 loci, but primary chondrosarcomas typically do not. To evaluate promoter methylation (which is an epigenetic gene silencing mechanism) of EXT1 and EXT2, we performed methylation-specific polymerase chain reaction (PCR) for 20 chondrosarcoma cases (12 primary, 3 secondary to osteochondroma, 2 secondary to enchondromatosis, 2 extraskeletal ordinary, and 1 clear cell) and in five cell lines. In addition, mutation analysis of the EXT1 and EXT2 coding regions was performed using PCR-single-strand conformation polymorphism and sequencing analysis for 12 of the 20 chondrosarcoma cases (8 primary, 1 secondary to enchondromatosis, 1 secondary to osteochondroma, and 2 extraskeletal ordinary) and five cell lines. Promoter methylation of EXT1 and EXT2 was not detected in any of the cases, and both EXT1 and EXT2 were expressed in all cell lines. Two missense mutations in EXT2 (D227E and R299H) were detected among the chondrosarcoma cases. When considering tumor development in primary chondrosarcoma, we should include mutations in EXT2, along with the status of other members of the EXT gene family.

AB - Germline mutation and functional loss of EXT1 or EXT2 are commonly found in multiple osteochondromas and predispose to the development of chondrosarcoma. Mutations of EXT1 and EXT2 have rarely been detected in sporadic secondary chondrosarcomas from osteochondroma; these frequently display loss of heterozygosity at the EXT1 and EXT2 loci, but primary chondrosarcomas typically do not. To evaluate promoter methylation (which is an epigenetic gene silencing mechanism) of EXT1 and EXT2, we performed methylation-specific polymerase chain reaction (PCR) for 20 chondrosarcoma cases (12 primary, 3 secondary to osteochondroma, 2 secondary to enchondromatosis, 2 extraskeletal ordinary, and 1 clear cell) and in five cell lines. In addition, mutation analysis of the EXT1 and EXT2 coding regions was performed using PCR-single-strand conformation polymorphism and sequencing analysis for 12 of the 20 chondrosarcoma cases (8 primary, 1 secondary to enchondromatosis, 1 secondary to osteochondroma, and 2 extraskeletal ordinary) and five cell lines. Promoter methylation of EXT1 and EXT2 was not detected in any of the cases, and both EXT1 and EXT2 were expressed in all cell lines. Two missense mutations in EXT2 (D227E and R299H) were detected among the chondrosarcoma cases. When considering tumor development in primary chondrosarcoma, we should include mutations in EXT2, along with the status of other members of the EXT gene family.

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