Met proto-oncogene juxtamembrane rare variations in mouse and humans: differential effects of Arg and Cys alleles on mouse lung tumorigenesis.
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.
Zaffaroni
Daniela
D
Department of Experimental Oncology, Istituto Nazionale Tumori, Via G Venezian 1, Milan, Italy.
Spinola
Monica
M
Galvan
Antonella
A
Falvella
F Stefania
FS
Pazzaglia
Simonetta
S
Saran
Anna
A
Mancuso
Maria Teresa
MT
Galbiati
Federica
F
Pignatiello
Carmen
C
Cabrera
Wafa
W
Ibanez
Olga
O
Manenti
Giacomo
G
Dragani
Tommaso A
TA
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
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