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Met proto-oncogene juxtamembrane rare variations in mouse and humans: differential effects of Arg and Cys alleles on mouse lung tumorigenesis

descriptionPublicationkeyboard_double_arrow_right Article 13 Dec 2004 English Publisher:Springer Science and Business Media LLCJournal:Oncogene, volume 24, pages 1,084-1,090 (issn: 0950-9232, eissn: 1476-5594,

Authors: Carmen Pignatiello; Simonetta Pazzaglia; M. Mancuso; Daniela Zaffaroni; Federica Galbiati; Giacomo Manenti; Anna Saran; +6 Authors

doi: 10.1038/sj.onc.1208324

pmid: 15592501

Met proto-oncogene juxtamembrane rare variations in mouse and humans: differential effects of Arg and Cys alleles on mouse lung tumorigenesis

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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.

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Keywords

Multifactorial Inheritance, Lung Neoplasms, Genetic Linkage, DNA Mutational Analysis, Molecular Sequence Data, Mice, Inbred Strains, Adenocarcinoma, Arginine, Proto-Oncogene Mas, Disease Models, Animal, Mice, Cell Transformation, Neoplastic, Carcinoma, Non-Small-Cell Lung, Animals, Humans, Genetic Predisposition to Disease, Amino Acid Sequence, Cysteine, Alleles, Germ-Line Mutation

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