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

George A. Calin, Maria Grazia Di Iasio, Elisabetta Caprini, Igor Vorechovsky, Pier Giorgio Natali, Gabriella Sozzi, Carlo M. Croce, Giuseppe Barbanti-Brodano, Giandomenico Russo, Massimo Negrini

Research output: Contribution to journalArticlepeer-review

Abstract

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

Original languageEnglish
Pages (from-to)1191-1195
Number of pages5
JournalOncogene
Volume19
Issue number9
Publication statusPublished - Feb 24 2000

Keywords

  • Human neoplasms
  • Mutations
  • PPP2R1A
  • PPP2R1B

ASJC Scopus subject areas

  • Molecular Biology
  • Cancer Research
  • Genetics

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