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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Acknowledgements
We thank Silvia Giordano for the gift of Met (B-2) antibody and GTL16 cells. This work was funded in part by grants from Associazione and Fondazione Italiana Ricerca Cancro (AIRC and FIRC) and Compagnia di San Paolo, Torino, Italy, and from the European Commission (Association Contract No. F14PCT950008a).
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Sequence data are available from GenBank under accession numbers AY439333, AY544984, AY551821, AY551822, AY558815, AY558816, AY558817, AY558818, AY558819, AY558820
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Zaffaroni, D., Spinola, M., Galvan, A. et al. Met proto-oncogene juxtamembrane rare variations in mouse and humans: differential effects of Arg and Cys alleles on mouse lung tumorigenesis. Oncogene 24, 1084–1090 (2005). https://doi.org/10.1038/sj.onc.1208324
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DOI: https://doi.org/10.1038/sj.onc.1208324
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