Infrequent mutations of the PPP2R1A and PPP2R1B genes in patients with ovarian cancer

Wang,Feng; Zou,Yang; Liu,Fa‑Ying; Yu,Xiao‑Hong; Huang,Huang; Zhang,Nan; Qi,Ying‑Ying; Liu,Rong‑Fang; Liu,Xiao‑Yan; Chen, Jia; Huang,Ou‑Ping; He,Ming

doi:10.3892/mmr.2013.1416

Infrequent mutations of the PPP2R1A and PPP2R1B genes in patients with ovarian cancer

Authors:
- Feng Wang
- Yang Zou
- Fa‑Ying Liu
- Xiao‑Hong Yu
- Huang Huang
- Nan Zhang
- Ying‑Ying Qi
- Rong‑Fang Liu
- Xiao‑Yan Liu
- Jia Chen
- Ou‑Ping Huang
- Ming He
View Affiliations

Affiliations: Key Laboratory of Women's Reproductive Health of Jiangxi Province, Jiangxi Provincial Maternal and Child Health Hospital, Nanchang, Jiangxi 330006, P.R. China, Department of Pathology, Jiangxi Provincial Maternal and Child Health Hospital, Nanchang, Jiangxi 330031, P.R. China, Department of Cardiothoracic Surgery, The First Affiliated Hospital of Nanchang University, Nanchang, Jiangxi 330006, P.R. China, Graduate School of Nanchang University, Nanchang, Jiangxi 330031, P.R. China, Jiangxi Provincial Cancer Institute, Jiangxi Provincial Cancer Hospital, Nanchang, Jiangxi 330029, P.R. China, Department of Pharmacology and Molecular Therapeutics, Nanchang University School of Pharmaceutical Science, Nanchang, Jiangxi 330006, P.R. China
Published online on: April 9, 2013 https://doi.org/10.3892/mmr.2013.1416
Pages: 1826-1830

Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )

Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )

Cited By (CrossRef): 0 citations Loading Articles...

Abstract

Protein phosphatase 2, regulatory subunit A, α (PPP2R1A) and β (PPP2R1B) are paralogous subunits of the heterotrimeric protein phosphatase 2 (PP2A) holoenzyme that catalyzes the dephosphorylation of target substrate proteins. Subtype‑specific PPP2R1A mutations have been frequently observed in ovarian and endometrial cancer. Mutations in the paralogous genes were frequently observed in human malignancies. Thus, the present study aimed to analyze the mutation frequencies of the paralogous PPP2R1A and PPP2R1B genes in patients with primary and secondary ovarian cancer. A total of 251 patients with primary (n=234) and secondary (n=17) ovarian cancer were analyzed for the presence of PPP2R1A and PPP2R1B mutations by direct sequencing. For PPP2R1A, a heterozygous, somatic mutation (c.771G>T, p.W257C) was identified in 1 out of 37 patients (2.7%) with primary ovarian endometrioid carcinoma. The mutant sample was that of a 46‑year‑old female, who was also diagnosed with ectopic endometriosis in the benign ovary. No PPP2R1A mutations were detected in the remaining 250 patients with ovarian cancer. For PPP2R1B, no mutations were detected in our samples. The results of this study suggested that PPP2R1A mutations are less common in Chinese patients with ovarian cancer when compared with European and American patients. Furthermore, our study also supported previous observations that PPP2R1B mutations were absent in ovarian cancer, suggesting that PPP2R1B mutations are not actively involved in the pathogenesis of ovarian cancer.

View Figures

View References

1	Slupe AM, Merrill RA and Strack S: Determinants for substrate specificity of protein phosphatase 2A. Enzyme Res. 2011:3987512011. View Article : Google Scholar : PubMed/NCBI
2	Ruediger R, Roeckel D, Fait J, Bergqvist A, Magnusson G and Walter G: Identification of binding sites on the regulatory A subunit of protein phosphatase 2A for the catalytic C subunit and for tumor antigens of simian virus 40 and polyomavirus. Mol Cell Biol. 12:4872–4882. 1992.
3	Xu Y, Xing Y, Chen Y, Chao Y, Lin Z, Fan E, Yu JW, Strack S, Jeffrey PD and Shi Y: Structure of the protein phosphatase 2A holoenzyme. Cell. 127:1239–1251. 2006. View Article : Google Scholar : PubMed/NCBI
4	Chen W, Arroyo JD, Timmons JC, Possemato R and Hahn WC: Cancer-associated PP2A Aalpha subunits induce functional haploinsufficiency and tumorigenicity. Cancer Res. 65:8183–8192. 2005. View Article : Google Scholar : PubMed/NCBI
5	Jones S, Wang TL, Shih IM, Mao TL, Nakayama K, Roden R, Glas R, Slamon D, Diaz LA Jr, Vogelstein B, et al: Frequent mutations of chromatin remodeling gene ARID1A in ovarian clear cell carcinoma. Science. 330:228–231. 2010. View Article : Google Scholar : PubMed/NCBI
6	McConechy MK, Anglesio MS, Kalloger SE, Yang W, Senz J, Chow C, Heravi-Moussavi A, Morin GB, Mes-Masson AM, et al; Australian Ovarian Cancer Study Group. Subtype-specific mutation of PPP2R1A in endometrial and ovarian carcinomas. J Pathol. 223:567–573. 2011. View Article : Google Scholar : PubMed/NCBI
7	Nagendra DC, Burke J III, Maxwell GL and Risinger JI: PPP2R1A mutations are common in the serous type of endometrial cancer. Mol Carcinog. 51:826–831. 2012. View Article : Google Scholar : PubMed/NCBI
8	Shih IM, Panuganti PK, Kuo KT, Mao TL, Kuhn E, Jones S, Velculescu VE, Kurman RJ and Wang TL: Somatic mutations of PPP2R1A in ovarian and uterine carcinomas. Am J Pathol. 178:1442–1447. 2011. View Article : Google Scholar : PubMed/NCBI
9	McConechy MK, Ding J, Cheang MC, Wiegand KC, Senz J, Tone AA, Yang W, Prentice LM, Tse K, Zeng T, et al: Use of mutation profiles to refine the classification of endometrial carcinomas. J Pathol. 228:20–30. 2012.PubMed/NCBI
10	Calin GA, di Iasio MG, Caprini E, Vorechovsky I, Natali PG, Sozzi G, Croce CM, Barbanti-Brodano G, Russo G and Negrini M: 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. Oncogene. 19:1191–1195. 2000. View Article : Google Scholar : PubMed/NCBI
11	Ruteshouser EC, Ashworth LK and Huff V: Absence of PPP2R1A mutations in Wilms tumor. Oncogene. 20:2050–2054. 2001. View Article : Google Scholar : PubMed/NCBI
12	Wang SS, Esplin ED, Li JL, Huang L, Gazdar A, Minna J and Evans GA: Alterations of the PPP2R1B gene in human lung and colon cancer. Science. 282:284–287. 1998. View Article : Google Scholar : PubMed/NCBI
13	Takagi Y, Futamura M, Yamaguchi K, Aoki S, Takahashi T and Saji S: Alterations of the PPP2R1B gene located at 11q23 in human colorectal cancers. Gut. 47:268–271. 2000. View Article : Google Scholar : PubMed/NCBI
14	Tamaki M, Goi T, Hirono Y, Katayama K and Yamaguchi A: PPP2R1B gene alterations inhibit interaction of PP2A-Abeta and PP2A-C proteins in colorectal cancers. Oncol Rep. 11:655–659. 2004.PubMed/NCBI
15	Suraweera N, Robinson J, Volikos E, Guenther T, Talbot I, Tomlinson I and Silver A: Mutations within Wnt pathway genes in sporadic colorectal cancers and cell lines. Int J Cancer. 119:1837–1842. 2006. View Article : Google Scholar : PubMed/NCBI
16	Wu R, Connolly DC, Ren X, Fearon ER and Cho KR: Somatic mutations of the PPP2R1B candidate tumor suppressor gene at chromosome 11q23 are infrequent in ovarian carcinomas. Neoplasia. 1:311–314. 1999. View Article : Google Scholar : PubMed/NCBI
17	Campbell IG and Manolitsas T: Absence of PPP2R1B gene alterations in primary ovarian cancers. Oncogene. 18:6367–6369. 1999. View Article : Google Scholar : PubMed/NCBI
18	Marsh A, Healey S, Lewis A, Spurdle AB, Kedda MA, Khanna KK, kConFab, Mann GJ, Pupo GM, Lakhani SR and Chenevix-Trench G: Mutation analysis of five candidate genes in familial breast cancer. Breast Cancer Res Treat. 105:377–389. 2007. View Article : Google Scholar : PubMed/NCBI
19	Chou HC, Chen CH, Lee HS, Lee CZ, Huang GT, Yang PM, Lee PH and Sheu JC: Alterations of tumour suppressor gene PPP2R1B in hepatocellular carcinoma. Cancer Lett. 253:138–143. 2007. View Article : Google Scholar : PubMed/NCBI
20	Hemmer S, Wasenius VM, Haglund C, Zhu Y, Knuutila S, Franssila K and Joensuu H: Alterations in the suppressor gene PPP2R1B in parathyroid hyperplasias and adenomas. Cancer Genet Cytogenet. 134:13–17. 2002. View Article : Google Scholar : PubMed/NCBI
21	Yeh LS, Hsieh YY, Chang JG, Chang WW, Chang CC and Tsai FJ: Mutation analysis of the tumor suppressor gene PPP2R1B in human cervical cancer. Int J Gynecol Cancer. 17:868–871. 2007. View Article : Google Scholar : PubMed/NCBI
22	Su F, Viros A, Milagre C, Trunzer K, Bollag G, Spleiss O, Reis-Filho JS, Kong X, Koya RC, Flaherty KT, et al: RAS mutations in cutaneous squamous-cell carcinomas in patients treated with BRAF inhibitors. N Engl J Med. 366:207–215. 2012. View Article : Google Scholar : PubMed/NCBI
23	Van Raamsdonk CD, Griewank KG, Crosby MB, Garrido MC, Vemula S, Wiesner T, Obenauf AC, Wackernagel W, Green G, Bouvier N, et al: Mutations in GNA11 in uveal melanoma. N Engl J Med. 363:2191–2199. 2010.PubMed/NCBI
24	Zou Y, Zeng Y, Zhang DF, Zou SH, Cheng YF and Yao YG: IDH1 and IDH2 mutations are frequent in Chinese patients with acute myeloid leukemia but rare in other types of hematological disorders. Biochem Biophys Res Commun. 402:378–383. 2010. View Article : Google Scholar : PubMed/NCBI
25	Zhu Y, Loukola A, Monni O, Kuokkanen K, Franssila K, Elonen E, Vilpo J, Joensuu H, Kere J, Aaltonen L and Knuutila S: PPP2R1B gene in chronic lymphocytic leukemias and mantle cell lymphomas. Leuk Lymphoma. 41:177–183. 2001. View Article : Google Scholar : PubMed/NCBI