Genomic Organization of a New Candidate Tumor Suppressor Gene, LRP1B

LRP1B is a novel candidate tumor suppressor gene that is inactivated by genetic and transcript alterations in nearly 50% of non-small-cell lung cancer cell lines. The gene-encoded protein is highly homologous to the gigantic lipoprotein receptor-related protein 1 (LRP1) that belongs to the family of low-density lipoprotein receptors. Using a combination of PCR-based genome walking and long-distance interexon PCR, we have determined the genomic organization of LRP1B and built a contiguous array of BAC clones spanning this gene. A total of 91 exons, varying in size from 77 bases (exon 87) to 1899 bases (exon 91), were identified in the more than 500-kb-long gene sequence. Comparative analysis of the genomic structures of LRP1B and the homologous LRP1 gene revealed a striking similarity in the location and sizes of their exons.