Low frequency of alterations of the alpha (PPP2R1A) and beta (PPP2R1B) isoforms of the subunit A of the serine-threonine phosphatase 2A in human neoplasms

The phosphatase 2A (PP2A) is one of the major cellular serine-threonine pho sphatases, It was recently shown that the gene encoding for the beta isofor m of its subunit A, PPP2R1B, is altered in human lung and colorectal carcin omas, suggesting a role in human tumorigenesis, Here, we report the detecti on of mutations in breast, lung carcinomas and melanomas in the genes of bo th alpha (PPP2R1A) and beta isoforms, Mutations affecting PPP2R1B were foun d in four breast carcinomas, while mutations in PPP2R1A were found in carci nomas of the breast and of the lung and in one melanoma. Most of the mutati ons affecting PPP2R1B were exons deletions, suggesting abnormal splicing. T hese splicing abnormalities were detected in tumor samples in the absence o f the normal splicing product, and were not found in several normal control s. In one case, a homozygous deletion present in tumor DNA, and not in the matched normal control was demonstrated. Mutations affecting the PPP2R1A ge ne were nucleotide substitutions changing highly conserved amino acids and one frame-shift. Although the frequency of alterations is low, the inclusio n of both isoforms of subunit A in the genes mutated in human cancer and th e addition of breast cancer to the list of neoplasms in which PPP2R1B is al tered, strengthen the potential role of PP2A in human tumorogenesis.