Refined mapping of two regions of loss of heterozygosity on chromosome band 11q23 in lung cancer

11q23-24 chromosome is a region containing frequent allelic loss (loss of h eterozygosity; LOH) in human cancers. To examine cancer-related allelic los s in the region between D11S940 and APOC3, we used 17 polymorphic markers a nd allotyped 28 lung cancer-derived cell lines and their corresponding matc hed lymphoblastoid cell lines. LOH was found in 71.4% (20/28) of the lung c ancer cell lines and was localized to Mo distinct minimal regions of loss. One region is bracketed by markers D11S1647 and NCAM2 and contains the gene encoding the beta isoform of the A subunit of the human protein phosphatas e 2A (PPP2R1B). Recently, mutations in this gene were described in lung and colon cancers, suggesting that PPP2R1B functions as a tumor-suppressor gen e. A second minimal region of loss was defined between markers D11S1792 and D11S1885, a region estimated to be less than I Mb, Thus, chromosome I I li kely harbors two sites of suppressor oncogene activity in lung cancer, one defined by the PPP2R1B gene and the second located telomeric to PPP2R1B. Th is study facilitates the identification and cloning of a second critical tu mor-suppressor gene involved in lung cancer, and possibly a variety of othe r cancers, on human chromosome band 11q23, (C) 1999 Wiley-Liss, Inc.