Alterations of the PPP2R1B gene located at 11q23 in human colorectal cancers

Background/aims-In 1998 the PPPZR1B gene encoding the A subunit of the seri ne/ threonine protein phosphatase was identified as a putative tumour suppr essor gene in lung and colon cancer in the chromosome region 11q22-24. The aim of the present study was to determine the type of alterations in primar y rectal cancers as well as colon cancers and the correlation between these alterations and clinicopathological data. Methods-Mutation analyses of the PPP2R1B gene sequence encoding the binding sites of the catalytic C subunit (Huntington elongation A subunit TOR (HEA T) repeats 11-15) and partial binding sites of the regulatory B subunit wer e carried out on cDNA samples from 30 primary colorectal cancer specimens a nd corresponding normal tissues using a combination of the polymerase chain reaction and subsequent direct DNA sequencing. Results-Five missense mutations producing amino acid substitutions were det ected in the four colon cancer cases (13.3%; four of 30 colorectal cancers) : (15)glycine (GGT) to alanine (GCT) and (499)leucine (TTA) to isoleucine ( ATA) in the same case, and (498)valine (GTG) to glutamic acid (GAG), (500)v aline (GTA) to glycine (GGA), and (365)serine (TCT) to proline (CCT). Of th ese five mutations, three (60%) were located in HEAT repeat 13 and four (80 %) showed T to other nucleotide substitutions. In addition, a normal polymo rphism, (478)leucine, was found. No correlation was found between these mut ations and clinicopathological data. Conclusion-Our results suggest that the PPP2R1B gene is one of the true tar gets at 11q23, and its inactivation is involved in the development of all t ypes of colorectal cancers.