DELETION MAPPING OF A PUTATIVE TUMOR-SUPPRESSOR GENE ON CHROMOSOME-4 IN MOUSE LUNG-TUMORS

Genetic and molecular studies have implicated the region of the alpha- interferon gene cluster on mouse chromosome 4 as the location of a put ative tumor suppressor gene. A region of homology on human chromosome 9p21-22 that is frequently deleted in multiple human cancers has recen tly been found to contain a candidate tumor suppressor gene called mul tiple tumor suppressor-1 (MTS1), which was previously shown to encode an inhibitor of cyclin-dependent kinase 4. We performed loss of hetero zygosity and deletion analyses to map the most commonly deleted region on chromosome 4 in F-1 hybrid mouse lung tumors. Ten simple sequence length polymorphism markers were analyzed with focus on the alpha-inte rferon region. Allelic losses were detected in 29 of 61 (48%) of the l ung adenocarcinomas but in only 1 of 38 (3%) of the lung adenomas exam ined. In most cases, the losses appeared to occur by nondisjunction. H owever, in three carcinomas, we detected homozygous deletions that ove rlapped at simple sequence length polymorphism marker D4MIT77. These d ata suggest a critical region of about 2 cM immediately distal to the alpha-interferon locus as the likely domain of a novel tumor suppresso r gene on mouse chromosome 4, the loss of which appears to be involved in the progression of mouse lung tumorigenesis.