The PPP2R1B gene, which encodes the beta isoform of the A subunit of the serine/threonine protein phosphatase 2A (PP2A), was identified as a putative human tumor suppressor gene. Sequencing of the PPP2R1B gene, located on human chromosome 11q22-24, revealed somatic alterations in 15% (5 out of 33) of primary lung tumors, 6% (4 out of 70) of lung tumor-derived cell lines, and 15% (2 out of 13) of primary colon tumors. One deletion mutation generated a truncated PP2A-Abeta protein that was unable to bind to the catalytic subunit of the PP2A holoenzyme. The PP2R1B gene product may suppress tumor development through its role in cell cycle regulation and cellular growth control.

The reading frame in the mRNA for the cytochrome b apoprotein in mitochondria of Physarum polycephalum is created by the insertion of 43 nucleotides in the mRNA relative to the mtDNA sequence encoding it (RNA editing). Most of these insertions (31) are single cytidines; however, single uridines are inserted at six sites, and the dinucleotides, CU and GC, are inserted at two sites and one site, respectively. These insertions create a 392-codon reading frame in the mature mRNA. The amino acid sequence inferred from this reading frame has similarity to cytochrome b apoproteins encoded by other mtDNAs. The insertions are quite evenly distributed throughout the length of the reading frame with an average spacing of 27 nucleotides. This mRNA has the highest percentage (23%) of noncytidine insertions of any Physarum RNA characterized to date. cDNAs corresponding to partially edited RNAs can be enriched by selective amplification. Some cDNAs that lack the GC dinucleotide insertion are fully edited at sites flanking the GC dinucleotide insertion site. Similarly some cDNAs lack the CT dinucleotide insertion or have a CC or TT insertion flanked by a fully edited sequence. These results imply that dinucleotide editing occurs by a process separate from the global insertion of cytidines.

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11q23-24 chromosome is a region containing frequent allelic loss (loss of heterozygosity; LOH) in human cancers. To examine cancer-related allelic loss in the region between D11S940 and APOC3, we used 17 polymorphic markers and allotyped 28 lung cancer-derived cell lines and their corresponding matched lymphoblastoid cell lines. LOH was found in 71.4% (20/28) of the lung cancer cell lines and was localized to two 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 phosphatase 2A (PPP2R1B). Recently, mutations in this gene were described in lung and colon cancers, suggesting that PPP2R1B functions as a tumor-suppressor gene. A second minimal region of loss was defined between markers D11S1792 and D11S1885, a region estimated to be less than I Mb. Thus, chromosome 11 likely harbors two sites of suppressor oncogene activity in lung cancer, one defined by the PPP2R1B gene and the second located telomeric to PPP2R1B. This study facilitates the identification and cloning of a second critical tumor-suppressor gene involved in lung cancer, and possibly a variety of other cancers, on human chromosome band 11q23.