Gastrointestinal stromal tumors (GISTs) are differentiated from other types of gastrointestinal mesenchymal tumors by the expression of c-kit receptor tyrosine kinase (KIT). More than 80% of GISTs have somatic mutations of the KIT gene and are considered to be caused by the mutations, a finding that allows the KIT inhibitor Imatinib mesylate (formerly known as STI-571) to be used successfully as a molecular target drug for GISTs. A few GISTs, however, do not show the gain-of-function mutations of KIT and, hence, are imatinib unresponsive. Japanese researchers found two types of gain-of-function mutations of PDGFR in 5 of 8 GISTs without KIT mutations but not in 10 GISTs with KIT mutations. The gain-of-function mutations of PDGFR gene might therefore play an important role on development of GISTs without KIT mutations. Read the editorial by William M. Grady as appeared on Gastroenterology 125(3):967-978, September 2003. |