Biopolym. Cell. 2015; 31(3):218-225.
13q Deletions detected by fluorescence in situ hybridization for diagnosis and prognosis of chronic lymphoproliferative neoplasms
1Sitko V. V., 2Misharina J. A., 1Minchenko J. M., 1Poluben L. O., 1Dmitrenko O. O., 1Silaiev Y. O., 1Kostyukova N. I., 1Tkachenko O. V., 1Tovstogan A. O., 1Polyanska V. M., 1Lyashenko L. O., 1Bebeshko V. G.
  1. State Institution "National Research Center for Radiation Medicine, NAMS of Ukraine"
    53, Melnykova Str., Kyiv, Ukraine, 04050
  2. Bogomolets National Medical University
    13, T. Shevchenko Blvd., Kiev, Ukraine, 01601


Aim. Determination of deletion of the long arm of chromosome 13 in the patients with chronic lymphocytic leukemia, diffuse large B-cell lymphoma and multiple myeloma to provide prognostic assessments of Chronic Lymphoproliferative Neoplasms (CLPN) sub-variants progression, and early detection of therapy resistant cases and relapses of CLPN. Methods. Preparations of bone marrow cells from all patients (n = 115) with CLPN were studied. Fluorescence in situ hybridization was performed using commercial test Vysis LSI D13S319 (13q14.3) Spectrum Orange/ Vysis LSI 13q34 Spectrum Green FISH probe kit (Abbott Molecular, USA). Results. The molecular cytogenetic investigations have revealed deletions of 13q in 38 % of the patients with CLPN. We also present a clinical case where the deletion of 13q is detected along with other cytogenetic aberrations that significantly impair a disease prognosis. Conclusion. The analysis of deletions of the long arm of chromosome 13 is an important diagnostic and prognostic criterion, which assists to optimizes the treatment of the patients with CLPN.
Keywords: chronic lymphoproliferative neoplasms, chronic lymphocytic leukemia, multiple myeloma, diffuse large B-cell lymphoma, 13q deletions, fluorescence in situ hybridization


[1] Fluorescence in situ hybridization (FISH) protocols and applications. Eds. Bridger JM, Volpi EV. Springer, 2010. 451 p.
[2] Dal Bo M, Rossi FM, Rossi D, Deambrogi C, Bertoni F, Del Giudice I, Palumbo G, Nanni M, Rinaldi A, Kwee I, Tissino E, Corradini G, Gozzetti A, Cencini E, Ladetto M, Coletta AM, Luciano F, Bulian P, Pozzato G, Laurenti L, Forconi F, Di Raimondo F, Marasca R, Del Poeta G, Gaidano G, Fo? R, Guarini A, Gattei V. 13q14 deletion size and number of deleted cells both influence prognosis in chronic lymphocytic leukemia. Genes Chromosomes Cancer. 2011;50(8):633-43.
[3] Rinaldi A, Mian M, Chigrinova E, Arcaini L, Bhagat G, Novak U, Rancoita PM, De Campos CP, Forconi F, Gascoyne RD, Facchetti F, Ponzoni M, Govi S, Ferreri AJ, Mollejo M, Piris MA, Baldini L, Soulier J, Thieblemont C, Canzonieri V, Gattei V, Marasca R, Franceschetti S, Gaidano G, Tucci A, Uccella S, Tibiletti MG, Dirnhofer S, Tripodo C, Doglioni C, Dalla Favera R, Cavalli F, Zucca E, Kwee I, Bertoni F. Genome-wide DNA profiling of marginal zone lymphomas identifies subtype-specific lesions with an impact on the clinical outcome. Blood. 2011;117(5):1595-604.
[4] Scandurra M, Mian M, Greiner TC, Rancoita PM, De Campos CP, Chan WC, Vose JM, Chigrinova E, Inghirami G, Chiappella A, Baldini L, Ponzoni M, Ferreri AJ, Franceschetti S, Gaidano G, Montes-Moreno S, Piris MA, Facchetti F, Tucci A, Nomdedeu JF, Lazure T, Lambotte O, Uccella S, Pinotti G, Pruneri G, Martinelli G, Young KH, Tibiletti MG, Rinaldi A, Zucca E, Kwee I, Bertoni F. Genomic lesions associated with a different clinical outcome in diffuse large B-Cell lymphoma treated with R-CHOP-21. Br J Haematol. 2010;151(3):221-31.
[5] Nelson M, Perkins SL, Dave BJ, Coccia PF, Bridge JA, Lyden ER, Heerema NA, Lones MA, Harrison L, Cairo MS, Sanger WG. An increased frequency of 13q deletions detected by fluorescence in situ hybridization and its impact on survival in children and adolescents with Burkitt lymphoma: results from the Children's Oncology Group study CCG-5961. Br J Haematol. 2010;148(4):600-10.
[6] Fonseca R, Bergsagel PL, Drach J, Shaughnessy J, Gutierrez N, Stewart AK, Morgan G, Van Ness B, Chesi M, Minvielle S, Neri A, Barlogie B, Kuehl WM, Liebisch P, Davies F, Chen-Kiang S, Durie BG, Carrasco R, Sezer O, Reiman T, Pilarski L, Avet-Loiseau H; International Myeloma Working Group. International Myeloma Working Group molecular classification of multiple myeloma: spotlight review. Leukemia. 2009;23(12):2210-21.
[7] Eid OM, Eid MM, Kayed HF, Mahmoud WM, Mousafa SS, Ismail MM, Abdeen DM. Detection of cytogenetics abnormalities in chronic lymphocytic leukemia using FISH technique and their prognostic impact. Gulf J Oncolog. 2014;1(15):68-75.
[8] Lenz G, Wright GW, Emre NC, Kohlhammer H, Dave SS, Davis RE, Carty S, Lam LT, Shaffer AL, Xiao W, Powell J, Rosenwald A, Ott G, Muller-Hermelink HK, Gascoyne RD, Connors JM, Campo E, Jaffe ES, Delabie J, Smeland EB, Rimsza LM, Fisher RI, Weisenburger DD, Chan WC, Staudt LM. Molecular subtypes of diffuse large B-cell lymphoma arise by distinct genetic pathways. Proc Natl Acad Sci U S A. 2008;105(36):13520-5.
[9] Bogusz AM, Baxter RH, Currie T, Sinha P, Sohani AR, Kutok JL, Rodig SJ. Quantitative immunofluorescence reveals the signature of active B-cell receptor signaling in diffuse large B-cell lymphoma. Clin Cancer Res. 2012;18(22):6122-35.
[10] Wada M, Okamura T, Okada M, Teramura M, Masuda M, Motoji T, Mizoguchi H. Delineation of the frequently deleted region on chromosome arm 13q in B-cell non-Hodgkin's lymphoma. Int J Hematol. 2000;71(2):159-66.
[11] Jekarl DW, Min CK, Kwon A, Kim H, Chae H, Kim M, Lim J, Kim Y, Han K. Impact of genetic abnormalities on the prognoses and clinical parameters of patients with multiple myeloma. Ann Lab Med. 2013;33(4):248-54.
[12] Gao X, Li C, Zhang R, Yang R, Qu X, Qiu H, Xu J, Lu H, Li J, Chen L. Fluorescence in situ hybridization analysis of chromosome aberrations in 60 Chinese patients with multiple myeloma. Med Oncol. 2012;29(3):2200-6.
[13] Biran N, Jagannath S, Chari A. Risk stratification in multiple myeloma, part the significance of genetic risk factors in the era of currently available therapies. Clin Adv Hematol Oncol. 2013;11(9):578-83.
[14] Zhou Y, Barlogie B, Shaughnessy JD Jr. The molecular characterization and clinical management of multiple myeloma in the post-genome era. Leukemia. 2009;23(11):1941-56.
[15] Oh S, Koo DH, Kwon MJ, Kim K, Suh C, Min CK, Yoon SS, Shin HJ, Jo DY, Kwak JY, Kim JS, Sohn SK, Joo YD, Eom HS, Kim SH, Kim YS, Kim C, Mun YC, Kim H, Lee DS, Lee JH; Korean Multiple Myeloma Working Party (KMMWP). Chromosome 13 deletion and hypodiploidy on conventional cytogenetics are robust prognostic factors in Korean multiple myeloma patients: web-based multicenter registry study. Ann Hematol. 2014;93(8):1353-61.
[16] Swerdlow SH, Campo E, Harris NL, Jaffe ES, Pileri SA, Stein H, Thiele J, Vardiman JW. WHO Classification of tu­mo­urs of haematopoietic and lymphoid tissues. World He­alth Organization, 2008. 439 p.
[17] Glantz S. Primer of Biostatistics McGraw-Hill Education Medical; 7 edition 2011; 320 p.
[18] Wolff DJ, Bagg A, Cooley LD, Dewald GW, Hirsch BA, Jacky PB, Rao KW, Rao PN; Association for Molecular Pathology Clinical Practice Committee; American College of Medical Genetics Laboratory Quality Assurance Committee. Guidance for fluorescence in situ hybridization testing in hematologic disorders. J Mol Diagn. 2007;9(2):134-43.
[19] Chang YH, Park J, Kim HC, Chun HK, Kim YR, Kim M, Han K, Lee JH, Lee KH, Cho HI, Lee YS, Lee DS. Korean patients with chronic lymphocytic leukemia show the similar types of chromosomal aberrations as those in Europe and North America. Leuk Res. 2006;30(6):695-9.
[20] Degheidy HA, Gadalla SM, Farooqui MZ, Abbasi F, Arthur DC, Bauer SR, Wilson WH, Wiestner A, Stetler-Stevenson MA, Marti GE. Bcl-2 level as a biomarker for 13q14 deletion in CLL. Cytometry B Clin Cytom. 2013;84(4):237-47.
[21] Caraway NP, Thomas E, Khanna A, Payne L, Zhang HZ, Lin E, Keating MJ, Katz RL. Chromosomal abnormalities detected by multicolor fluorescence in situ hybridization in fine-needle aspirates from patients with small lymphocytic lymphoma are useful for predicting survival. Cancer. 2008;114(5):315-22.
[22] Havelange V, Ameye G, Th?ate I, Callet-Bauchu E, Mugneret F, Michaux L, Dastugue N, Penther D, Barin C, Collonge-Rame MA, Baranger L, Terr? C, Nadal N, Lippert E, La? JL, Cabrol C, Tigaud I, Herens C, Hagemeijer A, Raphael M, Libouton JM, Poirel HA; GFCH (Groupe Francophone de Cytog?n?tique H?matologique). Patterns of genomic aberrations suggest that Burkitt lymphomas with complex karyotype are distinct from other aggressive B-cell lymphomas with MYC rearrangement. Genes Chromosomes Cancer. 2013;52(1):81-92.
[23] Durak BA, Akay OM, Sungar G, Bademci G, Aslan V, Caferler J, Ozdemir M, Cilingir O, Artan S, G?lba? Z. Conventional and molecular cytogenetic analyses in Turkish patients with multiple myeloma. Turk J Haematol. 2012;29(2):135-42.
[24] Gole L, Lin A, Chua C, Chng WJ. Modified cIg-FISH protocol for multiple myeloma in routine cytogenetic laboratory practice. Cancer Genet. 2014;207(1-2):31-4.
[25] Wolff DJ, Bagg A, Cooley LD, Dewald GW, Hirsch BA, Jacky PB, Rao KW, Rao PN; Association for Molecular Pathology Clinical Practice Committee; American College of Medical Genetics Laboratory Quality Assurance Committee. Guidance for fluorescence in situ hybridization testing in hematologic disorders. J Mol Diagn. 2007;9(2):134-43.