1. ¹Department of Experimental Oncology, Istituto Nazionale Tumori, Via G Venezian 1, Milan, Italy
2. ²ENEA CR Casaccia, Rome, Italy
3. ³Institute Butantan, Sao Paulo, Brazil

Correspondence: TA Dragani, E-mail: dragani@istitutotumori.mi.it

Received 1 July 2004; Revised 13 October 2004; Accepted 20 October 2004; Published online 13 December 2004.

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.