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

Abstract

The human RON gene (MST1R) 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.

Blocking tumorigenic activities of colorectal cancer cells by a splicing RON receptor variant defective in the tyrosine kinase domain

“…The cDNA molecular cloning confirmed that ROND170 was formed by alternative pre-mRNA splicing, eliminating exon 19 that encodes 46 amino acids belonging to the kinase domain. 31 Our current data confirm that this is the case. This deletion resulted in the reading-frame shift, causing the C-terminal truncation and eliminating the functional docking site.…”

Blocking tumorigenic activities of colorectal cancer cells by a splicing RON receptor variant defective in the tyrosine kinase domain

“…The cDNA molecular cloning confirmed that ROND170 was formed by alternative pre-mRNA splicing, eliminating exon 19 that encodes 46 amino acids belonging to the kinase domain. 31 Our current data confirm that this is the case. This deletion resulted in the reading-frame shift, causing the C-terminal truncation and eliminating the functional docking site.…”

Hypermethylation of Ron proximal promoter associates with lack of full-length Ron and transcription of oncogenic short-Ron from an internal promoter

“…Others and we reported the existence of sfRon, which although quite low in expression, was found in normal tissues and cancer cell lines (Ronsin et al, 1993;Angeloni et al, 2000;Bardella et al, 2004). Both forms of Ron were implicated in cell growth and motility, although with possible functional differences as suggested by the positive selection of both forms across evolution (murine Stk is also transcribed as a full-length and short-form, Persons et al, 1999).…”

RON(MST1R)is a novel prognostic marker and therapeutic target for gastroesophageal adenocarcinoma

“……”

Blocking tumorigenic activities of colorectal cancer cells by a splicing RON receptor variant defective in the tyrosine kinase domain

“…The cDNA molecular cloning confirmed that ROND170 was formed by alternative pre-mRNA splicing, eliminating exon 19 that encodes 46 amino acids belonging to the kinase domain. 31 Our current data confirm that this is the case. This deletion resulted in the reading-frame shift, causing the C-terminal truncation and eliminating the functional docking site.…”

Hypermethylation of Ron proximal promoter associates with lack of full-length Ron and transcription of oncogenic short-Ron from an internal promoter

“…Others and we reported the existence of sfRon, which although quite low in expression, was found in normal tissues and cancer cell lines (Ronsin et al, 1993;Angeloni et al, 2000;Bardella et al, 2004). Both forms of Ron were implicated in cell growth and motility, although with possible functional differences as suggested by the positive selection of both forms across evolution (murine Stk is also transcribed as a full-length and short-form, Persons et al, 1999).…”

RON(MST1R)is a novel prognostic marker and therapeutic target for gastroesophageal adenocarcinoma

“……”

Blocking tumorigenic activities of colorectal cancer cells by a splicing RON receptor variant defective in the tyrosine kinase domain

“…The cDNA molecular cloning confirmed that ROND170 was formed by alternative pre-mRNA splicing, eliminating exon 19 that encodes 46 amino acids belonging to the kinase domain. 31 Our current data confirm that this is the case. This deletion resulted in the reading-frame shift, causing the C-terminal truncation and eliminating the functional docking site.…”

Hypermethylation of Ron proximal promoter associates with lack of full-length Ron and transcription of oncogenic short-Ron from an internal promoter

“…Others and we reported the existence of sfRon, which although quite low in expression, was found in normal tissues and cancer cell lines (Ronsin et al, 1993;Angeloni et al, 2000;Bardella et al, 2004). Both forms of Ron were implicated in cell growth and motility, although with possible functional differences as suggested by the positive selection of both forms across evolution (murine Stk is also transcribed as a full-length and short-form, Persons et al, 1999).…”

RON(MST1R)is a novel prognostic marker and therapeutic target for gastroesophageal adenocarcinoma

“……”