Frequent allelic deletion at a novel locus on chromosome 5 in human lung cancer.

Abstract

Frequent allelic deletions in tumor cells are indicative of the inactivation of tumor suppressor genes. Recently, we isolated the single-copy sequence del-27 (I. Wieland, M. Böhm, and S. Bogatz, Proc. Natl. Acad. Sci. USA, 89: 9705-9709, 1992). Here we show that del-27 detects a restriction fragment length polymorphism that allows examination for loss of heterozygosity (LOH) in tumor specimens. LOH at the del-27 locus occurred in 57% (4 of 7) of the informative lung carcinomas independent of the histopathological differentiation grade. LOH for exon 11 of the APC gene occurred in 71% (5 of 7) of the informative cases but was not associated with LOH at the del-27 locus. The del-27 sequence was localized to chromosome 5p13-5q14, proximal to the MCC/APC region, using a somatic cell hybrid panel. Together with our previous finding that del-27 is deleted homozygously in a lung carcinoma cell line, these results suggest that del-27 is linked closely to a novel putative tumor suppressor gene.