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  • Discovery of genetic alterations in human neoplasms of the gene encoding for the PPP2R1A and PPP2R1B isoforms of the subunit A of the serine-threonine phosphatase 2A

Discovery of genetic alterations in human neoplasms of the gene encoding for the PPP2R1A and PPP2R1B isoforms of the subunit A of the serine-threonine phosphatase 2A

The phosphatase 2A (PP2A) is one of the major cellular serine-threonine phosphatases. It was recently shown that the gene encoding for the beta isoform of its subunit A, PPP2R1B, is altered in human lung and colorectal carcinomas, suggesting a role in human tumorigenesis. In the course of this project, we reported the detection of mutations in breast, lung carcinomas and melanomas in the genes of both alpha (PPP2R1A) and beta isoforms.

Mutations affecting PPP2R1B were found in four breast carcinomas, while mutations in PPP2R1A were found in carcinomas of the breast and of the lung and in one melanoma. Most of the mutations affecting PPP2R1B were exons deletions, suggesting abnormal splicing. These splicing abnormalities were detected in tumor samples in the absence of the normal splicing product, and were not found in several normal controls. In one case, a homozygous deletion present in tumor DNA, and not in the matched normal control was demonstrated.

Mutations affecting the PPP2R1A gene were nucleotide substitutions changing highly conserved amino acids and one frame-shift. Although the frequency of alterations is low, the inclusion of both isoforms of subunit A in the genes mutated in human cancer and the addition of breast cancer to the list of neoplasms in which PPP2R1B is altered, strengthen the potential role of PP2A in human tumorigenesis.

The result has been reported in a well-recognized international scientific journal. At present, the use of the result and its expected benefits are limited because of the low frequency at which this alteration is detected and the lack of association with clinical parameters.

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