Influence of various types of receptor tyrosine kinase gene mutations in pathogenesis of GISTs

在来源于KII基因纯合突变小鼠培养的肥大细胞的永生化肥大细胞系中激活的信号转导系统与来源于KII基因纯合突变小鼠培养的肥大细胞中激活的信号转导系统不同。该永生化肥大细胞系存在c-kit基因的额外突变，伊马替尼和尼洛替尼可有效抑制家族性GIST中新发现的跨膜结构域生殖系c-kit基因功能获得性突变的激活。我们还发现，与传统的胞外结构域c-kit基因突变相比，伊马替尼和尼洛替尼可有效抑制散发性GIST中新发现的胞外结构域c-kit基因突变的激活。

Signal transduction system activated in immortalized mast cell line which is derived from cultured mast cells of knock-in mice with germline homozygous mutation at kinase domain II was different from that in cultured mast cells of knock-in mice with germline homozygous mutation. The immortalized mast cell line had an additional mutation in the c-kit gene.Activation of newly found juxtamembrane domain germline c-kit gene gain-of-function mutation in familial GISTs was effectively inhibited by imatinib and nilotinib. We also found that activation of newly found extracellular domain c-kit gene mutation in sporadic GISTs is effectively inhibited by imatinib and nilotinib, compared to that of conventional extracellular domain c-kit gene mutation.