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Chromosomal DNA balance in human stem cell line 4BL

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Abstract

Ploidy of a chromosome set and some regular structural aberrations in the new human 4BL cell line by passage 205 have been characterized in the previous cytogenetic studies. The purpose of this study was to investigate, using the array CGH and FISH methods, the nature of regular monosomies in particular homologous pairs. Structural aberrations were detected in all the chromosome pairs distinguished as monosomies according to classical cytogenetic analyses. The most notable alterations have been detected in chromosomes 2, 4, 10, 13, and 17. Massive genetic material losses were a probable cause for the monosomy of chromosomes 4, 10, 13, and 17. The monosomy of the second pair of chromosomes was caused by a substantial transformation in one of the homologs typified as multiple duplications and the formation of a derivative—der(2)t(2;?)(q21;?). The application of array CGH aided us in identifying the regions of structural aberrations in chromosomes 2, 4, 10, 13, and 17, that allowed a more accurate identification with the use of the multicolor FISH method. The obtained results confirm the hypothesis concerning a coordinated emergence of deletions and duplications and their stabilizing effect on transformed chromosomes.

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References

  1. Chandra, T., Ewels, P.A., Schoenfelder, S., Furlan-Magaril, M., Wingett, S.W., Kirschner, K., Thuret, J.Y., Andrews, S., Fraser, P., and Reik, W., Global reorganization of the nuclear landscape in senescent cells, Cell Rep., 2015, vol. 10, no. 4, pp. 471–483.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  2. Oh, J.H., Kim, Y.J., Moon, S., Nam, H.Y., Jeon, J.P., Lee, J.H., Lee, J.Y., and Cho, Y.S., Genotype instability during long-term subculture of lymphoblastoid cell lines, J. Hum. Genet., 2013, vol. 58, no. 1, pp. 16–20.

    Article  CAS  PubMed  Google Scholar 

  3. Pihan, G.A., Centrosome dysfunction contributes to chromosome instability, chromoanagenesis, and genome reprograming in cancer, Front. Oncol., 2013, vol. 3, p. 277.

    Google Scholar 

  4. Stepanenko, A.A. and Kavsan, V.M., Immortalization and malignant transformation of eukaryotic cells, Cytol. Genet., 2012, vol. 46, no. 2, pp. 96–129.

    Article  Google Scholar 

  5. wwwlgcstandards-atccorg/

  6. Lukash, L.L., Iatsyshyna, A.P., Kushniruk, V.O., and Pidpala, O.V., Reprogramming of human adult somatic cells in vitro, in Factors of Experimental Evolution, Kyiv: Logos, 2011, vol. 11, pp. 493–498.

    Google Scholar 

  7. Kushniruk, V.O., Ruban, T.P., and Lukash, L.L., Morphological and growth peculiarities of new human cell line 4BL, in Factors in Experimental Evolution, Kyiv: Logos, 2011, vol. 13, pp. 315–319.

    Google Scholar 

  8. Macewicz, L.L., Kushniruk, V.O., Iatsyshyna, A.P., Kotsarenko, K.V., Lylo, V.V., Akopyan, G.R., Huleyuk, N.L., Mykytenko, D.M., and Lukash, L.L., Correlation the level of mutagenesis with expression of reparative enzyme O6-metylhuanin DNA methyltransferase (MGMT) during establishment of cell lines in vitro, Biopolym. Cell, 2013, vol. 29, no. 6, pp. 485–492.

    Article  Google Scholar 

  9. Kushniruk, V.O., Kochubei, T.P., Matsevich, L.L., Ruban, T.P., and Lukash, L.L., Study of karyotype of the new human cell line 4VL6 after long-term cultivation in vitro, in Advances and Problems in Genetics, Breeding, and Biotechnology, Kyiv: Logos, 2012, vol. 3, pp. 313–318.

    Google Scholar 

  10. Akopyan, H.R., Huleyuk, N.L., Kushniruk, V.O., Mykytenko, D.O., Iatsyshyna, A.P., and Lukash, L.L., Comparative analysis of the karyotype of new human cell line 4BL at long cultivation. Ploidity of the chromosomal set, Cytol. Genet., 2013, vol. 47, no. 5, pp. 305–317.

    Article  Google Scholar 

  11. Freshney, R.I., Culture of Animal Cells: a Manual of Basic Technique and Specialized Applications, 6th ed., Wiley Blackwell, 2011.

    Google Scholar 

  12. Hungerford, D.A., Leukocytes cultured from small inocula of whole blood and the preparation of metaphase chromosomes by treatment with hypotonic KCl, Stain. Technol., 1965, vol. 40, no. 6, pp. 333–338.

    Article  CAS  PubMed  Google Scholar 

  13. Moorhead, P.S., Nowell, P.C., Mellman, W.I., Battips, D.M., and Hungerford, D.A., Chromosome preparations of leukocytes cultured from human peripheral blood, Exp. Cell Res., 1960, vol. 20, no. 3, pp. 613–616.

    Article  CAS  PubMed  Google Scholar 

  14. Seabright, M., A rapid banding technique for human chromosomes, Lancet, 1971, vol. 2, no. 7731, pp. 971–972.

    Article  CAS  PubMed  Google Scholar 

  15. ICSN 2013. An International System for Human Cytogenetic Nomenclature, Shaff, L.G., McGowan-Jordan, J., and Schmid, M., Eds., Basel: Karger, 2013.

  16. Riegel, M., Human molecular cytogenetics: from cells to nucleotides, Genet. Mol. Biol., 2014, vol. 37, no. 1, pp. 194–209.

    Article  PubMed  Google Scholar 

  17. Evangelidou, P., Alexandrou, A., Moutafi, M., Ioannides, M., Antoniou, P., Koumbaris, G., Kallikas, I., Velissariou, V., Sismani, C., and Patsalis, P.C., Implementation of high resolution whole genome array CGH in the prenatal clinical setting: advantages, challenges, and review of the literature, Biomed. Res. Int., 2013, vol. 2013, Article ID346762.

  18. Wan, T.S. and Ma, E.S., Molecular cytogenetics: an indispensable tool for cancer diagnosis, Chang Gung Med. J., 2012, vol. 35, no. 2, pp. 96–110.

    PubMed  Google Scholar 

  19. Yin, A., Lu, J., Liu, C., Guo, L., Wu, J., Mai, M., Zhong, Y., and Zhang, X., A prenatal missed diagnosed case of submicroscopic chromosomal abnormalities by karyotyping: the clinical utility of array-based CGH in prenatal diagnostics, Mol. Cytogenet., 2014, vol. 7, p. 26.

    Article  PubMed  PubMed Central  Google Scholar 

  20. Bi, W., Borgan, C., Pursley, A.N., Hixson, P., Shaw, C.A., Bacino, C.A., Lalani, S.R., Patel, A., Stankiewicz, P., Lupski, J.R., Beaudet, A.L., and Cheung, S.W., Comparison of chromosome analysis and chromosomal microarray analysis: what is the value of chromosome analysis in today’s genomic array era?, Genet. Med., 2013, vol. 15, no. 6, pp. 450–457.

    Article  PubMed  Google Scholar 

  21. Kushniruk, V.O., Akopyan, H.R., Mykytenko, D.O., Huleyuk, N.L., Zukin, V.D., and Lukash, L.L., The dynamic of ultrastructural pathologies of the karyotype of human stem cell line 4BL, revealed by array CGH, Factors in Experimental Evolution, 2015, vol. 16, pp. 216–221.

    Google Scholar 

  22. Weleber, R.G., Verma, R.S., Kimberling, W.J., Fieger, H.G., and Iubs, H.A., Duplication-deficiency of the short arm of chromosome 8 following artificial insemination, Ann. Genet., 1976, vol. 19, no. 4, pp. 241–247.

    CAS  PubMed  Google Scholar 

  23. Gorinati, M., Caufin, D., Minelli, A., Memo, L., Gaspardo, G., and Dodero, A., Inv dup (8) (p21.1–22.1): further case report and a new hypothesis on the origin of the chromosome abnormality, Clin. Genet., 1991, vol. 39, no. 1, pp. 55–59.

    Article  CAS  PubMed  Google Scholar 

  24. Pettenati, M.J., Rao, P.N., Phelan, M.C., Grass, F., Rao, K.W., Cosper, P., Carroll, A.J., Elder, F., Smith, J.L., Higgins, M.D., et al., Paracentric inversions in humans: a review of 446 paracentric inversions with presentation of 120 new cases, Am. J. Med. Genet., 1995, vol. 55, no. 2, pp. 171–187.

    Article  CAS  PubMed  Google Scholar 

  25. Stankiewicz, P. and Lupski, J.R., Genome architecture, rearrangements and genomic disorders, Trends Genet., 2002, vol. 18, no. 2, pp. 74–82.

    CAS  PubMed  Google Scholar 

  26. Shaffer, L.G. and Lupski, J.R., Molecular mechanisms for constitutional chromosomal rearrangements in humans, Ann. Rev. Genet., 2000, vol. 34, pp. 297–329.

    Article  CAS  PubMed  Google Scholar 

  27. Rowe, L.R., Lee, J.Y., Recto, L., Kaminsky, E.B., Brothman, A.R., Martin, C.L., and South, S.T., U-type exchange is the most frequent mechanism for inverted duplication with terminal deletion rearrangements, J. Med. Genet., 2009, vol. 46, no. 10, pp. 694–702.

    Article  CAS  PubMed  Google Scholar 

  28. Tassano, E., Alpigiani, M.G., Salvati, P., Gimelli, S., Lorini, R., and Gimelli, G., Molecular cytogenetic characterization of the first reported case of an inv dup (4p)(p15.1-pter) with a concomitant 4q35.1-qter deletion and normal parents, Gene, 2012, vol. 511, no. 2, pp. 338–340.

    Article  CAS  PubMed  Google Scholar 

  29. Horvath, J.E., Bailey, J.A., Locke, D.P., and Eichler, E.E., Lessons from the human genome: transitions between euchromatin and heterochromatin, Hum. Mol. Genet., 2001, vol. 10, no. 20, pp. 2215–2223.

    Article  CAS  PubMed  Google Scholar 

  30. Eastmond, D.A., Schuler, M., Frantz, C., Chen, H., Parks, R., Wang, L., and Hasegawa, L., Characterization and mechanisms of chromosomal alterations induced by benzene in mice and humans, Res. Rep. Health Eff. Inst., 2001, vol. 103, pp. 1–68.

    PubMed  Google Scholar 

  31. Rapini, N., Lidano, R., Pietrosanti, S., Vitiello, G., Grimaldi, C., Postorivo, D., Nardone, M., Del Bufalo, F., Brancati, F., and Manca BittiM.L., De novo 13q13.3-21.31 deletion involving RB1 gene in a patient with hemangioendothelioma of the liver, Ital. J. Pediatr., 2014, vol. 40, pp. 1–5.

  32. Mitter, D., Ullmann, R., Muradyan, A., Klein-Hitpass, L., Kanber, D., Ounap, K., Kaulisch, M., and Lohmann, D., Genotype-phenotype correlations in patients with retinoblastoma and interstitial 13q deletions, Eur. J. Hum. Genet., 2011, vol. 19, no. 9, pp. 947–958.

    Article  PubMed  PubMed Central  Google Scholar 

  33. Thienpont, B., Vermeesch, J.R., and Fryns, J.P., 25 Mb deletion of 13q13.3-q21.31 in a patient without retinoblastoma, Eur. J. Med. Genet., 2005, vol. 48, no. 3, pp. 363–366.

  34. Bui, T.H., Vetro, A., Zuffardi, O., and Shaffer, L.G., Current controversies in prenatal diagnosis 3: is conventional chromosome analysis necessary in the postarray CGH era?, Prenatal. Diagn., 2011, vol. 31, no. 3, pp. 235–243.

    Article  Google Scholar 

  35. Bonaglia, M.C., Giorda, R., Poggi, G., Raggi, M.E., Rossi, E., Baroncini, A., Giglio, S., Borgatti, R., and Zuffardi, O., Inverted duplications are recurrent rearrangements always associated with a distal deletion: description of a new case involving 2q, Eur. J. Hum. Genet., 2000, vol. 8, no. 8, pp. 597–603.

    Article  CAS  PubMed  Google Scholar 

  36. Kibe, T., Mori, Y., Okanishi, T., Shimojima, K., Yokochi, K., and Yamamoto, T., Two concurrent chromosomal aberrations involving interstitial deletion in 1q24.2q25.2 and inverted duplication and deletion in 10q26 in a patient with stroke associated with antithrombin deficiency and a patent foramen ovale, Am. J. Med. Genet., 2011, vol. 155A, no. 1, pp. 215–220.

    Article  PubMed  Google Scholar 

  37. Xiao, B., Ji, X., Xing, Y., Jiang, W.T., Zhang, J.M., and Tao, J., Inverted duplication and deletion of 10q25q26 in a patient without any obvious skeletal anomalies, Mol. Syndromol., 2012, vol. 3, no. 4, pp. 185–189.

    CAS  PubMed  PubMed Central  Google Scholar 

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Correspondence to H. R. Akopyan.

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Original Ukrainian Text © H.R. Akopyan, V.O. Kushniruk, D.O. Mykytenko, N.L. Huleuk, Yu. Kremenskaya, L.L. Lukash, 2016, published in Tsitologiya i Genetika, 2016, Vol. 50, No. 4, pp. 79–89.

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Akopyan, H.R., Kushniruk, V.O., Mykytenko, D.O. et al. Chromosomal DNA balance in human stem cell line 4BL. Cytol. Genet. 50, 257–266 (2016). https://doi.org/10.3103/S0095452716040022

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