title: Met proto-oncogene juxtamembrane rare variations in mouse and humans: differential effects of Arg and Cys alleles on mouse lung tumorigenesis.
abstract: Analysis of seven candidate genes mapping in the 1-Mb region of the mouse pulmonary adenoma resistance 4 (Par4) locus revealed a single amino-acid change, consisting in a nonconservative Arg968Cys variation in the juxtamembrane domain of the Met proto-oncogene-encoded protein. The BALB/c strain (resistant allele) carried the Arg allele, whereas the SWR/J mouse strain (Par4-susceptible allele) carried the Cys variation, recently proven to functionally modulate tumorigenesis. Seven genetic linkage crosses herein analysed and six crosses reported in the literature pointed to the candidacy of the Met gene for Par4. Analysis of genomic DNA of 126 lung adenocarcinoma patients for the Met juxtamembrane domain revealed the same Arg/Cys variation at the mouse homologous position in one patient; two other patients carried additional variants in the same domain, suggesting a potential role for rare MET juxtamembrane variants in human lung cancer.
authors.affiliation: Department of Experimental Oncology, Istituto Nazionale Tumori, Via G Venezian 1, Milan, Italy.
authors.forename: Daniela
authors.initials: D
authors.lastname: Zaffaroni
authors.forename: Monica
authors.initials: M
authors.lastname: Spinola
authors.forename: Antonella
authors.initials: A
authors.lastname: Galvan
authors.forename: F Stefania
authors.initials: FS
authors.lastname: Falvella
authors.forename: Simonetta
authors.initials: S
authors.lastname: Pazzaglia
authors.forename: Anna
authors.initials: A
authors.lastname: Saran
authors.forename: Maria Teresa
authors.initials: MT
authors.lastname: Mancuso
authors.forename: Federica
authors.initials: F
authors.lastname: Galbiati
authors.forename: Carmen
authors.initials: C
authors.lastname: Pignatiello
authors.forename: Wafa
authors.initials: W
authors.lastname: Cabrera
authors.forename: Olga
authors.initials: O
authors.lastname: Ibanez
authors.forename: Giacomo
authors.initials: G
authors.lastname: Manenti
authors.forename: Tommaso A
authors.initials: TA
authors.lastname: Dragani
mesh_terms: D000230:Adenocarcinoma / Q000235:genetics* / Q000503:physiopathology*; D000483:Alleles; D000595:Amino Acid Sequence; D000818:Animals; D001120:Arginine; D002289:Carcinoma, Non-Small-Cell Lung / Q000235:genetics* / Q000503:physiopathology*; D002471:Cell Transformation, Neoplastic; D003545:Cysteine; D004252:DNA Mutational Analysis; D004195:Disease Models, Animal; D008040:Genetic Linkage; D020022:Genetic Predisposition to Disease; D018095:Germ-Line Mutation; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics* / Q000503:physiopathology*; D051379:Mice; D008815:Mice, Inbred Strains; D008969:Molecular Sequence Data; D020412:Multifactorial Inheritance; D000090063:Proto-Oncogene Mas; D011518:Proto-Oncogene Proteins / Q000235:genetics*; D019859:Proto-Oncogene Proteins c-met; D017978:Receptors, Growth Factor / Q000235:genetics*; D018179:Receptors, Thrombin; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: C000715470:MAS1 protein, human; D000090063:Proto-Oncogene Mas; D011518:Proto-Oncogene Proteins; D017978:Receptors, Growth Factor; D018179:Receptors, Thrombin; D001120:Arginine; C491743:MET protein, human; D019859:Proto-Oncogene Proteins c-met; C112908:protease-activated receptor 4; D003545:Cysteine