GENETIC-MAPPING OF LUNG-CANCER MODIFIER LOCI SPECIFICALLY AFFECTING TUMOR INITIATION AND PROGRESSION

Mouse inbred strains with inherited predisposition and resistance to l ung cancer provide a tool for the dissection of the complex genetics o f this disease, In the present report, we have crossed the BALB/c with the SWR/J strain and performed whole-genome scanning for loci affecti ng lung tumor development in their F-2 progeny, Both parental strains carry the pulmonary adenoma susceptibility 1 (Pas1) locus, a major lot us affecting predisposition to lung cancer in mice. On distal chromoso me 18 and on centromere of chromosome 6, we have mapped two pulmonary adenoma resistance loci (Par2 and Par4, respectively), which reduce lu ng tumor multiplicity strongly, up to 15-fold, Par2 and Par4, however, do not affect lung tumor size, which is instead controlled by an addi tional locus that we have mapped on the central region of chromosome 4 , We designated this locus as ''pulmonary adenoma progression 1'' (Pap g1), because it specifically modifies lung tumor size but not multipli city, The present results, therefore, provide evidence for the existen ce of cancer modifier loci acting on specific stages of lung tumorigen esis.