Gene structure of the human receptor tyrosine kinase RON and mutation analysis in lung cancer samples

The human RON gene (MSTIR) maps to 3p21.3, a region frequently altered in l ung cancer and other malignancies. It encodes a receptor tyrosine kinase (R TK) closely related to MET, whose mutations are associated with neoplasia. We investigated whether RON might be involved in the development or progres sion of lung cancer. We first determined the exon-intron structure of the g ene by direct sequencing of RON cosmid DNA and PCR products containing intr onic sequences, and then developed primers suitable for mutation analysis b y the single-strand conformation polymorphism (SSCP) method. Twenty coding exons were characterized, ail but the first one small (average size: 170 bp ), a feature shared with other RTK genes. We performed SSCP analysis of RON in small and non-small cell lung cancer samples, upon detection of its exp ression in a sample of lung cancer cell lines. A mutation (T915C: L296P) wa s found in an adenocarcinoma specimen. Several single nucleotide polymorphi sms were also found. The panel of intron-anchored primers developed in this work will be useful for mutation analysis of the RON gene in different typ es of human tumors. (C) 2000 Wiley-Liss, Inc.