LRP-DIT, a putative endocytic receptor gene, is frequently inactivated in non-small cell lung cancer cell lines

A variety of studies suggest that allelic losses at chromosome 2q are assoc iated with aggressive behavior of various forms of human neoplasia. Using a probe to detect homozygous deletions on chromosome 2921.2 in kidney and bl adder cancer fell lines, we identified a new candidate tumor suppressor gen e, lipoprotein receptor-related protein-deleted in tumors (LRP-DIT). The pr edicted LRP-DIT product of 4599 amino acids has extensive homology to a gig antic receptor, LRP1, which mediates endocytosis of multiple proteins from the cell surface. Homozygous deletions in LRP-DIT were detected in 17% (4 o f 23) of non-small cell lung cancer (NSCLC) cell lines. The expression of o nly abnormal transcripts missing portions of the LRP-DIT sequence was demon strated in an additional 30% (11 of 36) of NSCLC lines. Finally, a missense mutation at codon 3157 was detected in one of four NSCLC Lines tested for the large open reading frame. In contrast, no LRP-DIT alterations were iden tified in a major fraction of SCLC cell lines, indicating that this gene is preferentially inactivated in one histological type of lung cancer. Our da ta suggest that inactivation of LRP-DIT occurs in at least 40% of NSCLC lin es and thus may play an important role in tumorigenesis of NSCLCs.