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

Daniela Zaffaroni, Monica Spinola, Antonella Galvan, F. Stefania Falvella, Simonetta Pazzaglia, Anna Saran, Maria Teresa Mancuso, Federica Galbiati, Carmen Pignatiello, Wafa Cabrera, Olga Ibanez, Giacomo Manenti, Tommaso A. Dragani

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19 Citations (Scopus)


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. © 2005 Nature Publishing Group All rights reserved.
Original languageEnglish
Pages (from-to)1084 - 1090
Number of pages7
Issue number6
Publication statusPublished - 3 Feb 2005
Externally publishedYes


All Science Journal Classification (ASJC) codes

  • Molecular Biology
  • Cancer Research
  • Genetics

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