分子生物学の立場からみたGISTの特性と臨床への応用

Molecular Characteristics of GISTs and the Possibility of Their Clinical Application

要旨　gastrointestinal stromal tumor(GIST)が高頻度にc-kit遺伝子の機能獲得性突然変異を持つことは，GISTの発生にc-kit遺伝子の突然変異が関与している可能性を示唆し，KITレセプターを含めいくつかの分子マーカーがGISTとカハールの介在細胞(interstitial cells of Cajal；ICCs)に共通して発現していることは，GISTがICCs由来の腫瘍である可能性を示唆している．germlineにc-kit遺伝子の機能獲得性突然変異を持つ家系の患者にICCsの過形成を基盤とした多発性GISTがみられる事実は，これらの2つの可能性を裏付けている．今後はGISTに密接に関わるc-kit遺伝子・KITレセプターを標的とした臨床応用が期待される．

　Gastrointestinal stromal tumors (GISTs) frequently have gain-of-function mutation of the c-kit gene, suggesting that the mutation is one of the causes of development of GISTs. GISTs and interstitial cells of Cajal (ICCs) share the several phenotypic characteristics including KIT receptor expression, suggesting that GISTs originate from ICCs. These two suggestions are supported by the fact that the patients with germline gain-of-function mutation of the c-kit gene have multiple GISTs associated with diffuse ICC hyperplasia. The molecules of the c-kit gene and KIT receptor may be unique indicators for prediction of the patient's prognosis and treatment of the malignant GISTs.