Molecular Pathology of Gastrointestinal Stromal Tumors and Implications for Treatment and Prognosis

摘要

Hhe recognition in the early 1990s that 95% of gastrointestinal stromal tumors (GISTs) express KIT on the cellular surface prompted investigation into the pathogenic role of KIT, leading to the discovery of activating mutations within its gene in 1998.1 The KIT proto-oncogene resides on the long arm of chromosome 4 and encodes the KIT protein, a transmembrane receptor tyrosine kinase whose ligand is known as a stem cell factor. Subsequent investigation has demonstrated gain-of-function mutations of KIT in approximately 80% of GISTs, resulting in constitutive activation of the tyrosine kinase domain. Of these mutations, 75% occur in Exon 11, which encodes a juxtamembrane domain; 20% occur in Exon 9, which encodes the C-terminal extracellular domain, and the remaining mutations are found in Exons 13 and 17, which encode parts of the tyrosine kinase domain.