Gain-of-Function Mutations of c- <i>kit</i> in Human Gastrointestinal Stromal Tumors

  • Seiichi Hirota
    S. Hirota, K. Hashimoto, G. M. Tunio, Y. Kitamura, Department of Pathology, Osaka University Medical School, Yamada-oka 2-2, Suita 565, Japan.
  • Koji Isozaki
    S. Hirota, K. Hashimoto, G. M. Tunio, Y. Kitamura, Department of Pathology, Osaka University Medical School, Yamada-oka 2-2, Suita 565, Japan.
  • Yasuhiro Moriyama
    S. Hirota, K. Hashimoto, G. M. Tunio, Y. Kitamura, Department of Pathology, Osaka University Medical School, Yamada-oka 2-2, Suita 565, Japan.
  • Koji Hashimoto
    S. Hirota, K. Hashimoto, G. M. Tunio, Y. Kitamura, Department of Pathology, Osaka University Medical School, Yamada-oka 2-2, Suita 565, Japan.
  • Toshirou Nishida
    S. Hirota, K. Hashimoto, G. M. Tunio, Y. Kitamura, Department of Pathology, Osaka University Medical School, Yamada-oka 2-2, Suita 565, Japan.
  • Shingo Ishiguro
    S. Hirota, K. Hashimoto, G. M. Tunio, Y. Kitamura, Department of Pathology, Osaka University Medical School, Yamada-oka 2-2, Suita 565, Japan.
  • Kiyoshi Kawano
    S. Hirota, K. Hashimoto, G. M. Tunio, Y. Kitamura, Department of Pathology, Osaka University Medical School, Yamada-oka 2-2, Suita 565, Japan.
  • Masato Hanada
    S. Hirota, K. Hashimoto, G. M. Tunio, Y. Kitamura, Department of Pathology, Osaka University Medical School, Yamada-oka 2-2, Suita 565, Japan.
  • Akihiko Kurata
    S. Hirota, K. Hashimoto, G. M. Tunio, Y. Kitamura, Department of Pathology, Osaka University Medical School, Yamada-oka 2-2, Suita 565, Japan.
  • Masashi Takeda
    S. Hirota, K. Hashimoto, G. M. Tunio, Y. Kitamura, Department of Pathology, Osaka University Medical School, Yamada-oka 2-2, Suita 565, Japan.
  • Ghulam Muhammad Tunio
    S. Hirota, K. Hashimoto, G. M. Tunio, Y. Kitamura, Department of Pathology, Osaka University Medical School, Yamada-oka 2-2, Suita 565, Japan.
  • Yuji Matsuzawa
    S. Hirota, K. Hashimoto, G. M. Tunio, Y. Kitamura, Department of Pathology, Osaka University Medical School, Yamada-oka 2-2, Suita 565, Japan.
  • Yuzuru Kanakura
    S. Hirota, K. Hashimoto, G. M. Tunio, Y. Kitamura, Department of Pathology, Osaka University Medical School, Yamada-oka 2-2, Suita 565, Japan.
  • Yasuhisa Shinomura
    S. Hirota, K. Hashimoto, G. M. Tunio, Y. Kitamura, Department of Pathology, Osaka University Medical School, Yamada-oka 2-2, Suita 565, Japan.
  • Yukihiko Kitamura
    S. Hirota, K. Hashimoto, G. M. Tunio, Y. Kitamura, Department of Pathology, Osaka University Medical School, Yamada-oka 2-2, Suita 565, Japan.

抄録

<jats:p> Gastrointestinal stromal tumors (GISTs) are the most common mesenchymal tumors in the human digestive tract, but their molecular etiology and cellular origin are unknown. Sequencing of c- <jats:italic>kit</jats:italic> complementary DNA, which encodes a proto-oncogenic receptor tyrosine kinase (KIT), from five GISTs revealed mutations in the region between the transmembrane and tyrosine kinase domains. All of the corresponding mutant KIT proteins were constitutively activated without the KIT ligand, stem cell factor (SCF). Stable transfection of the mutant c- <jats:italic>kit</jats:italic> complementary DNAs induced malignant transformation of Ba/F3 murine lymphoid cells, suggesting that the mutations contribute to tumor development. GISTs may originate from the interstitial cells of Cajal (ICCs) because the development of ICCs is dependent on the SCF-KIT interaction and because, like GISTs, these cells express both KIT and CD34. </jats:p>

収録刊行物

  • Science

    Science 279 (5350), 577-580, 1998-01-23

    American Association for the Advancement of Science (AAAS)

被引用文献 (566)*注記

もっと見る

キーワード

詳細情報

問題の指摘

ページトップへ