A locus on chromosome 8 controlling tumor regionality-a new type of tumor diversity in the mouse lung.

Regional specificity of lung tumor formation has rarely been studied in mouse or human. By using crosses of strains semi-congenic for lung cancer susceptibility locus Sluc20, we have analyzed the genetic influences of Sluc20 and 5 other loci on tumor regionality in the mouse lung. We have mapped Sluc20 to a 27.92-MB proximal region of chromosome 8 and found that it controls the number and load of only those tumors that surround or are directly adjacent to the bronchi or bronchioli (peribronchial tumors). These tumors lie outside the bronchial basement membrane and tend to reach a larger size than the tumors at other locations in the lung. Similar to tumors of alveolar lineage at other locations, peribronchial tumors stain with SP-C but not CC10 antibody. The effects of Sluc20 alleles are additive because the number of peribronchial tumors in heterozygotes is intermediate. These findings show that tumor regionality in the mouse lung, which represents a novel level of lung tumor heterogeneity, is under specific genetic control. The identification of genes controlling lung tumor regionality will provide novel insights into the biology of lung tumors and potentially improve the possibilities of individualized prognosis and treatment in human lung cancer.