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 associated with aggressive behavior of various forms of human neoplasia. Using a probe to detect homozygous deletions on chromosome 2q21.2 in kidney and bladder cancer cell lines, we identified a new candidate tumor suppressor gene, lipoprotein receptor-related protein-deleted in tumors (LRP-DIT). The predicted LRP-DIT product of 4599 amino acids has extensive homology to a gigantic receptor, LRP1, which mediates endocytosis of multiple proteins from the cell surface. Homozygous deletions in LRP-DIT were detected in 17% (4 of 23) of non-small cell lung cancer (NSCLC) cell lines. The expression of only abnormal transcripts missing portions of the LRP-DIT sequence was demonstrated 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 identified in a major fraction of SCLC cell lines, indicating that this gene is preferentially inactivated in one histological type of lung cancer. Our data suggest that inactivation of LRP-DIT occurs in at least 40% of NSCLC lines and thus may play an important role in tumorigenesis of NSCLCs.
Liu
C X
CX
Department of Genetics, University of Pennsylvania School of Medicine, Philadelphia 19104, USA.
Musco
S
S
Lisitsina
N M
NM
Forgacs
E
E
Minna
J D
JD
Lisitsyn
N A
NA
D000595:Amino Acid Sequence; D001483:Base Sequence; D002289:Carcinoma, Non-Small-Cell Lung / Q000235:genetics*; D002874:Chromosome Mapping; D002889:Chromosomes, Human, Pair 2; D003062:Codon; D004705:Endocytosis; D017353:Gene Deletion; D016147:Genes, Tumor Suppressor; D005819:Genetic Markers; D006720:Homozygote; D006801:Humans; D026503:Low Density Lipoprotein Receptor-Related Protein-1; D008175:Lung Neoplasms / Q000235:genetics*; D008969:Molecular Sequence Data; D020125:Mutation, Missense; D016366:Open Reading Frames; D011971:Receptors, Immunologic / Q000235:genetics*; D014407:Tumor Cells, Cultured
D003062:Codon; D005819:Genetic Markers; D026503:Low Density Lipoprotein Receptor-Related Protein-1; D011971:Receptors, Immunologic