TY - JOUR
T1 - Met proto-oncogene juxtamembrane rare variations in mouse and humans
T2 - Differential effects of Arg and Cys alleles on mouse lung tumorigenesis
AU - Zaffaroni, Daniela
AU - Spinola, Monica
AU - Galvan, Antonella
AU - Falvella, F. Stefania
AU - Pazzaglia, Simonetta
AU - Saran, Anna
AU - Mancuso, Maria Teresa
AU - Galbiati, Federica
AU - Pignatiello, Carmen
AU - Cabrera, Wafa
AU - Ibanez, Olga
AU - Manenti, Giacomo
AU - Dragani, Tommaso A.
PY - 2005/2/3
Y1 - 2005/2/3
N2 - 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.
AB - 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.
KW - Cancer modifier loci
KW - Polygenic inheritance
KW - Susceptibility to disease
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U2 - 10.1038/sj.onc.1208324
DO - 10.1038/sj.onc.1208324
M3 - Article
C2 - 15592501
AN - SCOPUS:13944257764
VL - 24
SP - 1084
EP - 1090
JO - Oncogene
JF - Oncogene
SN - 0950-9232
IS - 6
ER -