Biopolym. Cell. 2015; 31(1):29-33.
Structure and Function of Biopolymers
Heterozygous deletions are main cause of expression alterations of PPM1M and PRICLE2 genes in human clear cell renal cell carcinomas
1Rudenko E. E., 1Lapska Y. V., 1Gerashchenko G. V., 2Stakhovsky E. O., 2Vikarchuk M. V., 1Kashuba V. I.
  1. Institute of Molecular Biology and Genetics, NAS of Ukraine
    150, Akademika Zabolotnoho Str., Kyiv, Ukraine, 03680
  2. National Cancer Institute
    33/43, Lomonosova Str., Kyiv, Ukraine, 03022

Abstract

Aim. To discover the mechanisms of the PPM1M and PRICKLE2 genes expression alterations in clear cell renal cell carcinomas. Methods. Study of the copy number was performed, using the quantitative PCR (Q-PCR). Results. Deletions of PPM1M were found in 55 % of cases, amplifications – in 17 % and in 28 % of samples there were no changes of the copy number. We found the deletions of PRICKLE2 in 50 % of samples, no changes of the copy number in 39 %, and amplifications in 11 % of cases. Conclusions. By the analysis of the gene copy number we have shown that homo- and heterozygous deletions are the main reason of changes in expression of the PPM1M and PRICKLE2 genes.
Keywords: clear cell renal cell carcinoma, heterozygous deletions, quantitative PCR, copy number analysis

References

[1] Cheville JC, Lohse CM, Zincke H, Weaver AL, Blute ML. Comparisons of outcome and prognostic features among histologic subtypes of renal cell carcinoma. Am J Surg Pathol. 2003;27(5):612-24.
[2] Bhat S. Role of surgery in advanced/metastatic renal cell carcinoma. Indian J Urol. 2010;26(2):167-76.
[3] Pavlovich CP, Schmidt LS, Phillips JL. The genetic basis of renal cell carcinoma. Urol Clin North Am. 2003;30(3):437-54.
[4] Dmitriev AA, Rudenko EE, Kudryavtseva AV, Krasnov GS, Gordiyuk VV, Melnikova NV, Stakhovsky EO, Kononenko OA, Pavlova LS, Kondratieva TT, Alekseev BY, Braga EA, Senchenko VN, Kashuba VI. Epigenetic alterations of chromosome 3 revealed by NotI-microarrays in clear cell renal cell carcinoma. Biomed Res Int. 2014;2014:735292.
[5] Senchenko VN, Kisseljova NP, Ivanova TA, Dmitriev AA, Krasnov GS, Kudryavtseva AV, Panasenko GV, Tsitrin EB, Lerman MI, Kisseljov FL, Kashuba VI, Zabarovsky ER. Novel tumor suppressor candidates on chromosome 3 revealed by NotI-microarrays in cervical cancer. Epigenetics. 2013;8(4):409-20.
[6] Dmitriev AA, Kashuba VI, Haraldson K, Senchenko VN, Pavlova TV, Kudryavtseva AV, Anedchenko EA, Krasnov GS, Pronina IV, Loginov VI, Kondratieva TT, Kazubskaya TP, Braga EA, Yenamandra SP, Ignatjev I, Ernberg I, Klein G, Lerman MI, Zabarovsky ER. Genetic and epigenetic analysis of non-small cell lung cancer with NotI-microarrays. Epigenetics. 2012;7(5):502-13.
[7] Kashuba V, Dmitriev AA, Krasnov GS, Pavlova T, Ignatjev I, Gordiyuk VV, Gerashchenko AV, Braga EA, Yenamandra SP, Lerman M, Senchenko VN, Zabarovsky E. NotI microarrays: novel epigenetic markers for early detection and prognosis of high grade serous ovarian cancer. Int J Mol Sci. 2012;13(10):13352-77.
[8] Rudenko EE, Gerashchenko GV, Lapska YV, Vozianov SO, Zgonnyk YM, Kashuba VI. PPM1M and PRICKLE2 are po­tential tumor suppressor genes in human clear-cell renal cell carcinoma. Biopolym Cell. 2014; 30(3):229–33.
[9] Henmi T, Amano K, Nagaura Y, Matsumoto K, Echigo S, Tamura S, Kobayashi T. A mechanism for the suppression of interleukin-1-induced nuclear factor kappaB activation by protein phosphatase 2Ceta-2. Biochem J. 2009;423(1):71-8.
[10] Katoh M. WNT/PCP signaling pathway and human cancer (review). Oncol Rep. 2005;14(6):1583-8.
[11] Speissel B, Beahrs OH, Hermanek P, Hutter RVP, Scheibe O. TNM atlas: illustrated guide to the TNM. pTNM classification of malignant tumours. Berlin New York: Springer-Verlag. 1989.
[12] Travis WD, Coby TV, Corrin B, Shimosato Y, Brambilla E. World Health Organization International Histological Clas­sification of Tumours; Histological typing of lung and ple­ural tumours. Berlin: Springer. 1999.
[13] Jung M, Ramankulov A, Roigas J, Johannsen M, Ringsdorf M, Kristiansen G, Jung K. In search of suitable reference genes for gene expression studies of human renal cell carcinoma by real-time PCR. BMC Mol Biol. 2007;8:47.
[14] Gerashchenko GV, Bogatyrova OO, Rudenko EE, Kondratov AG, Gordiyuk VV, Zgonnyk YM, Vozianov OF, Pavlova TV, Zabarovsky ER, Rynditch AV, Kashuba VI. Genetic and epigenetic changes of NKIRAS1 gene in human renal cell carcinomas. Exp Oncol. 2010;32(2):71-5.
[15] Senchenko VN, Liu J, Loginov W, Bazov I, Angeloni D, Seryogin Y, Ermilova V, Kazubskaya T, Garkavtseva R, Zabarovska VI, Kashuba VI, Kisselev LL, Minna JD, Lerman MI, Klein G, Braga EA, Zabarovsky ER. Discovery of frequent homozygous deletions in chromosome 3p21.3 LUCA and AP20 regions in renal, lung and breast carcinomas. Oncogene. 2004;23(34):5719-28.
[16] Shakir SM, Bryant KM, Larabee JL. Regulatory interactions of a virulence-associated serine. threonine phospha­tase-kinas
[17] Shi Y. Serine/threonine phosphatases: mechanism through structure. Cell. 2009;139(3):468-84.
[18] Dedinszki D, Kiss A, M?rk?sz L, M?rton A, T?th E, Sz?kely L, Erd?di F. Inhibition of protein phosphatase-1 and -2A decreases the chemosensitivity of leukemic cells to chemotherapeutic drugs. Cell Signal. 2015;27(2):363-72.
[19] Komaki K, Katsura K, Ohnishi M, Guang Li M, Sasaki M, Watanabe M, Kobayashi T, Tamura S. Molecular cloning of PP2Ceta, a novel member of the protein phosphatase 2C family. Biochim Biophys Acta. 2003;1630(2-3):130-7.
[20] Fanto M, McNeill H. Planar polarity from flies to vertebrates. J Cell Sci. 2004;117(Pt 4):527-33.
[21] Bastock R, Strutt H, Strutt D. Strabismus is asymmetrically localised and binds to Prickle and Dishevelled during Drosophila planar polarity patterning. Development. 2003;130(13):3007-14.