ALLELIC LOSS OF DISTAL CHROMOSOME-4 IN MOUSE LUNG-TUMORS LOCALIZE A PUTATIVE TUMOR-SUPPRESSOR GENE TO A REGION HOMOLOGOUS WITH HUMAN-CHROMOSOME 1P36

Loss of heterozygosity (LOH) of distal chromosome 4 was studied to loc alize a putative tumor suppressor gene in mouse lung neoplasia. Previo us studies have implicated this region and its homologue on human chro mosome 1p36-34 as sites of potential tumor suppressor genes. One hundr ed adenocarcinomas and 38 adenomas of the mouse lung mere examined for LOH using nine simple sequence length polymorphism markers in a polym erase chain reaction-based approach. Forty-four adenocarcinomas displa yed allele loss, all of which included losses at marker D4MIT54, which defined a critical region of 3 centiMorgans as the likely location of a putative tumor suppressor gene. In 58% of the tumors displaying LOH , all markers used in this study incurred allele loss. In contrast, re tention of heterozygosity was observed at all markers tested in each o f the adenomas studied, which suggests that the inactivation of this t umor suppressor gene participates in mouse lung tumor progression.