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Gene structure of the human receptor tyrosine kinase RON and mutation analysis in lung cancer samples
Author(s) -
Angeloni Debora,
DanilkovitchMiagkova Alla,
Ivanov Sergey V.,
Breathnach Richard,
Johnson Bruce E.,
Leonard Edward J.,
Lerman Michael I.
Publication year - 2000
Publication title -
genes, chromosomes and cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.754
H-Index - 119
eISSN - 1098-2264
pISSN - 1045-2257
DOI - 10.1002/1098-2264(2000)9999:9999<::aid-gcc1015>3.0.co;2-n
Subject(s) - exon , single strand conformation polymorphism , biology , gene , lung cancer , genetics , intron , cosmid , microbiology and biotechnology , mutation testing , coding region , mutation , cancer research , pathology , medicine
The human RON gene ( MST 1 R ) maps to 3p21.3, a region frequently altered in lung cancer and other malignancies. It encodes a receptor tyrosine kinase (RTK) closely related to MET , whose mutations are associated with neoplasia. We investigated whether RON might be involved in the development or progression of lung cancer. We first determined the exon‐intron structure of the gene by direct sequencing of RON cosmid DNA and PCR products containing intronic sequences, and then developed primers suitable for mutation analysis by the single‐strand conformation polymorphism (SSCP) method. Twenty coding exons were characterized, all 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 expression in a sample of lung cancer cell lines. A mutation (T915C: L296P) was found in an adenocarcinoma specimen. Several single nucleotide polymorphisms 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 types of human tumors. © 2000 Wiley‐Liss, Inc.