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Absence of PPP2R1A mutations in Wilms tumor

Abstract

Evidence from genetic linkage analysis indicates that a gene located at 19q13.4, FWT2, is responsible for predisposition to Wilms tumor in many Wilms tumor families. This region has also been implicated in the etiology of sporadic Wilms tumor through loss of heterozygosity analyses. The PPP2R1A gene, encoding the α isoform of the heterotrimeric serine/threonine protein phosphatase 2A (PP2A), is located within the FWT2 candidate region and is altered in breast and lung carcinomas. PPP2R1B, encoding the β isoform, is mutated in lung, colon, and breast cancers. These findings suggested that both PPP2R1A and PPP2R1B may be tumor suppressor genes. Additionally, PP2A is important in fetal kidney growth and differentiation and has an expression pattern similar to that of the Wilms tumor suppressor gene WT1. Since PPP2R1A was therefore a compelling candidate for the FWT2 gene, we analysed the coding region of PPP2R1A in DNA and RNA samples from affected members of four Wilms tumor families and 30 sporadic tumors and identified no mutations in PPP2R1A in any of these 34 samples. We conclude that PPP2R1A is not the 19q familial Wilms tumor gene and that mutation of PPP2R1A is not a common event in the etiology of sporadic Wilms tumor.

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Acknowledgements

The cooperation and help of patients and their physicians is greatly appreciated. We thank R Alam for excellent technical assistance and P Begin and D Sembera for sample collection. This work was supported in part by NCI grants CA78257, CA34936, CA16672, and a grant from the Kadoorie Foundation. A portion of this work was performed under the auspices of the US Department of Energy at Lawrence Livermore National Laboratory under Contract No. W-7405-ENG-48.

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Ruteshouser, E., Ashworth, L. & Huff, V. Absence of PPP2R1A mutations in Wilms tumor. Oncogene 20, 2050–2054 (2001). https://doi.org/10.1038/sj.onc.1204301

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