nodgoРоссийский журнал детской гематологии и онкологии (РЖДГиО)Russian Journal of Pediatric Hematology and Oncology2311-12672413-5496LTD “Graphica”10.21682/2311-1267-2019-6-1-11-19nodgo-467Research ArticleОригинальные исследованияПрогностическое значение наиболее частых цитогенетических перестроек при нейробластоме. Результаты Республиканского научно-практического центра детской онкологии, гематологии и иммунологии Республики БеларусьPrognostic value of the most frequent cytogenetic rearrangements in neuroblastoma. Results of the Republican Scientific and Practical Center for Pediatric Oncology, Hematology and Immunology of the Republic of BelarusПролесковскаяИ. В.ProleskovskayaI. V.

к.м.н., доцент, заведующая онкологическим инфекционным (гематологическим) отделением № 2 РНПЦ ДОГИ

Cand. of Sci. (Med.), Docent, Head of Oncological Infectious (Hematology) Department No. 2

proleskai@mail.ruВолочникЕ. В.ValochnikE. V.

научный сотрудник лаборатории молекулярно-генетических исследований РНПЦ ДОГИ

Researcher Laboratory of Molecular Genetic Studies

valochnikalena@gmail.comБукатВ. П.BukatV. P.

младший научный сотрудник лаборатории молекулярно-генетических исследований РНПЦ ДОГИ

Junior Researcher Laboratory of Molecular Genetic Studies

bukat_vera@mail.ruБыдановО. И.BydanovO. I.

ведущий инженер-программист РНПЦ ДОГИ

Lead Software Engineer

budanov@oncology.byКонопляН. Е.KonoplyaN. E.

д.м.н., профессор, заместитель директора по клинической работе РНПЦ ДОГИ

Dr. of Sci. (Med.), Professor, Deputy Director of Clinical Work

n.konoplya@mail.ruНГУ «Республиканский научно-практический центр детской онкологии, гематологии и иммунологии» Министерства здравоохранения Республики БеларусьБеларусьRepublican Scientific and Practical Center for Pediatric Oncology, Hematology and Immunology, Ministry of Health of the Republic of BelarusBelarusНГУ «Республиканский научно-практический центр детской онкологии, гематологии и иммунологии» Министерства здравоохранения Республики БеларусьБеларусьRepublican Scientific and Practical Center for Pediatric Oncology, Hematology and Immunology, Ministry of Health of the Republic of BelarusBelarus201911022019611119Copyright © Пролесковская И.В., Волочник Е.В., Букат В.П., Быданов О.И., Конопля Н.Е., 20192019Пролесковская И.В., Волочник Е.В., Букат В.П., Быданов О.И., Конопля Н.Е.Proleskovskaya I.V., Valochnik E.V., Bukat V.P., Bydanov O.I., Konoplya N.E.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://journal.nodgo.org/jour/article/view/467

Цель исследования – оценить частоту встречаемости наиболее частых цитогенетических перестроек при нейробластоме (НБ) и их корреляцию с клинико-биологическими характеристиками и исходом терапии в Республике Беларусь. Материалы и методы. Исследованы 280 пациентов с первично диагностируемой НБ с 10.10.2007 по 01.04.2018. Материалом для исследования послужили первичная опухоль или метастазы опухоли в костный мозг (поражение более 60 %) согласно критериям протокола. Исследование проводилось методом флуоресцентной гибридизации in situ. Результаты. Частота встречаемости таких цитогенетических аберраций, как MYCN-амплификация (20,1 %), делеция/дисбаланс 11q (19,7 %) и аберрации 1р (28 %) в исследуемой популяции соответствует данным литературы. Частота встречаемости gain17q (34,5 %) была ниже литературных данных. Статистически достоверно подтверждено негативное влияние на бессобытийную выживаемость (БСВ) пациентов с НБ наличие таких генетических аберраций в опухоли, как MYCN-амплификация, делеция/дисбаланс 11q, аберрации 1р. Статистически достоверно подтверждены более высокие показатели бессобытийной выживаемости для больных с околотриплоидным набором хромосом в опухоли по сравнению с околоди-/тетроплоидным (97 ± 3 % против 63 ± 5 %). Для пациентов, у которых в опухоли отсутствовали структурные аберрации, БСВ составила 75 ± 4 % против 51 ± 9 % в группе с аберрациями (р < 0,0001).

The purpose of the study is to assess the frequency of occurrence of the most frequent cytogenetic rearrangements in neuroblastoma (NB) and their correlation with clinical and biological characteristics and outcome of therapy in the Republic of Belarus. Materials and methods. 280 patients with primary diagnosed NB from 10.10.2007 to 01.04.2018 were studied. The material for the study was the primary tumor or tumor metastases in the bone marrow (damage more than 60 %) according to the criteria of the protocol. The study was conducted by the method of fluorescent hybridization in situ. Results. The frequency of occurrence of such cytogenetic aberrations as MYCN amplification (20.1 %), 11q deletion/imbalance (19.7 %) and 1p aberration (28%) in the studied population corresponds to literature data. The frequency of occurrence of gain17q (34.5 %) was lower than the literature data. The negative effect on event-free survival (EFS) of patients with NB was statistically confirmed and the presence of such genetic aberrations in the tumor, such as MYCN amplification, 11q deletion/imbalance, 1p aberration. Statistically reliably confirmed higher rates of event-free survival for patients with near-triloid set of chromosomes in the tumor, as compared with near-/tetroploid (97 ± 3 % versus 63 ± 5 %). For patients who lacked structural aberrations in the tumor, EFS was 75 ± 4 % versus 51 ± 9 % in the group with aberrations (p < 0.0001).

детинейробластомацитогенетические аберрацииFISHпрогнозchildrenneuroblastomacytogenetic aberrationsFISHprognosisReferencesSpitz R., Betts D.R., Simon T., Boensch M., Oestreich J., Niggli F.K., Ernestus K., Berthold F., Hero B. Favorable outcome of triploid neuroblastomas: a contribution to the special oncogenesis of neuroblastoma. Cancer Genet Cytogenet 2006;167:51–6.Spitz R., Betts D.R., Simon T., Boensch M., Oestreich J., Niggli F.K., Ernestus K., Berthold F., Hero B. Favorable outcome of triploid neuroblastomas: a contribution to the special oncogenesis of neuroblastoma. Cancer Genet Cytogenet 2006;167:51–6.doi: 10.1016/j.cancergencyto.2005.09.001.doi: 10.1016/j.cancergencyto.2005.09.001.Spitz R., Oberthuer A., Zapatka M., Brors B., Hero B., Ernestus K., Oestreich J., Fischer M., Simon T., Berthold F. Oligonucleotide arraybased comparative genomic hybridization (aCGH) of 90 neuroblastomas reveals aberration patterns closely associated with relapse pattern and outcome. Genes Chromosomes Cancer 2006;45(12):1130–42. doi: 10.1002/gcc.20376.Spitz R., Oberthuer A., Zapatka M., Brors B., Hero B., Ernestus K., Oestreich J., Fischer M., Simon T., Berthold F. Oligonucleotide arraybased comparative genomic hybridization (aCGH) of 90 neuroblastomas reveals aberration patterns closely associated with relapse pattern and outcome. Genes Chromosomes Cancer 2006;45(12):1130–42. doi: 10.1002/gcc.20376.Brodeur G.M. Neuroblastoma: Biological insights into a clinical enigma. Nat Rev Cancer 2003;3:203–16. doi: 10.1038/nrc1014.Brodeur G.M. Neuroblastoma: Biological insights into a clinical enigma. Nat Rev Cancer 2003;3:203–16. doi: 10.1038/nrc1014.Schwab M., Westermann F., Hero B., Berthold F. Neuroblastoma: Biology and molecular and chromosomal pathology. Lancet Oncol 2003;4(8):472–80. doi: 10.1016/S1470-2045(03)01166-5.Schwab M., Westermann F., Hero B., Berthold F. Neuroblastoma: Biology and molecular and chromosomal pathology. Lancet Oncol 2003;4(8):472–80. doi: 10.1016/S1470-2045(03)01166-5.Cohn S.L., Tweddle D.A. MYCN amplification remains prognostically strong 20 years after its “clinical debut”. Eur J Cancer 2004;40:2639–42. doi: 10.1016/j.ejca.2004.07.025.Cohn S.L., Tweddle D.A. MYCN amplification remains prognostically strong 20 years after its “clinical debut”. Eur J Cancer 2004;40:2639–42. doi: 10.1016/j.ejca.2004.07.025.Lau D.T., Flemming C.L., Gherardi S., Perini G., Oberthuer A., Fischer M., Juraeva D., Brors B., Xue C., Norris M.D., Marshall G.M., Haber M., Fletcher J.I., Ashton L.J. MYCN amplification confers enhanced folate dependence and methotrexate sensitivity in neuroblastoma. Oncotarget 2015;6(17):15510–23.Lau D.T., Flemming C.L., Gherardi S., Perini G., Oberthuer A., Fischer M., Juraeva D., Brors B., Xue C., Norris M.D., Marshall G.M., Haber M., Fletcher J.I., Ashton L.J. MYCN amplification confers enhanced folate dependence and methotrexate sensitivity in neuroblastoma. Oncotarget 2015;6(17):15510–23.doi: 10.18632/oncotarget.3732.doi: 10.18632/oncotarget.3732.Maris J.M., Weiss M.J., Guo C., Gerbing R.B., Stram D.O., White P.S., Hogarty M.D., Sulman E.P., Thompson P.M., Lukens J.N., Matthay K.K., Seeger R.C., Brodeur G.M. Loss of heterozygosityMaris J.M., Weiss M.J., Guo C., Gerbing R.B., Stram D.O., White P.S., Hogarty M.D., Sulman E.P., Thompson P.M., Lukens J.N., Matthay K.K., Seeger R.C., Brodeur G.M. Loss of heterozygosityat 1p36 independently predicts for disease progression but not decreased overall survival probability in neuroblastoma patients: a Children’s Cancer Group study. J Clin Oncol 2000;18:1888–99. doi: 10.1200/JCO.2000.18.9.1888.at 1p36 independently predicts for disease progression but not decreased overall survival probability in neuroblastoma patients: a Children’s Cancer Group study. J Clin Oncol 2000;18:1888–99. doi: 10.1200/JCO.2000.18.9.1888.Mazzocco K., Defferrari R., Sementa A.R., Garaventa A., Longo L., De Mariano M., Rosaria Esposito M., Negri F., Ircolo D., Viscardi E., Luksch R., D’Angelo P., Prete A., Castellano A., Massirio P., Erminio G., Gigliotti A.R., Tonini G.P., Conte M. Genetic abnormalities in adolescents and young adults with neuroblastoma: A report from the Italian Neuroblastoma Group. Pediatr Blood Cancer 2015;62(10):1725–32. doi: 10.1002/pbc.25552.Mazzocco K., Defferrari R., Sementa A.R., Garaventa A., Longo L., De Mariano M., Rosaria Esposito M., Negri F., Ircolo D., Viscardi E., Luksch R., D’Angelo P., Prete A., Castellano A., Massirio P., Erminio G., Gigliotti A.R., Tonini G.P., Conte M. Genetic abnormalities in adolescents and young adults with neuroblastoma: A report from the Italian Neuroblastoma Group. Pediatr Blood Cancer 2015;62(10):1725–32. doi: 10.1002/pbc.25552.Defferrari R., Mazzocco K., Ambros I.M., Ambros P.F., Bedwell C., Beiske K., Bernard J., Berbegall A.P., Bown N., Combaret V., Couturier J., Erminio G., Gambini C., Garaventa A., Gross N., Haupt R., Kohler J., Jeison M., Lunec J., Marques B., Martinsson T., Noguera R., Parodi S., Schleiermacher G., Tweddle D.A., Valent A., Van Roy N., Vicha A., Villamon E., Tonini G.P. Influence of segmental chromosome abnormalities on survival in children over the age of 12 months with unresectable localised peripheral neuroblastic tumours without MYCN amplification. Br J Cancer 2015;112(2):290–5. doi: 10.1038/bjc.2014.557.Defferrari R., Mazzocco K., Ambros I.M., Ambros P.F., Bedwell C., Beiske K., Bernard J., Berbegall A.P., Bown N., Combaret V., Couturier J., Erminio G., Gambini C., Garaventa A., Gross N., Haupt R., Kohler J., Jeison M., Lunec J., Marques B., Martinsson T., Noguera R., Parodi S., Schleiermacher G., Tweddle D.A., Valent A., Van Roy N., Vicha A., Villamon E., Tonini G.P. Influence of segmental chromosome abnormalities on survival in children over the age of 12 months with unresectable localised peripheral neuroblastic tumours without MYCN amplification. Br J Cancer 2015;112(2):290–5. doi: 10.1038/bjc.2014.557.Krona C., Ejeskär K., Abel F., Kogner P., Bjelke J., Björk E., Sjöberg R., Martinsson T. Screening for gene mutations in a 500 kb neuroblastoma tumor suppressor candidate region in chromosome 1p; mutation and stage-specific expression in UBE4B/UFD2. Oncogene 2003;22:2343–51. doi: 10.1038/sj.onc.1206324.Krona C., Ejeskär K., Abel F., Kogner P., Bjelke J., Björk E., Sjöberg R., Martinsson T. Screening for gene mutations in a 500 kb neuroblastoma tumor suppressor candidate region in chromosome 1p; mutation and stage-specific expression in UBE4B/UFD2. Oncogene 2003;22:2343–51. doi: 10.1038/sj.onc.1206324.Maris J.M., Guo C., Blake D., White P.S., Hogarty M.D., Thompson P.M., Rajalingam V., Gerbing R., Stram D.O., Matthay K.K., Seeger R.C., Brodeur G.M. Comprehensive analysis of chromosome 1p deletions in neuroblastoma. Med Pediatr Oncol 2001;36:32–6. doi: 10.1002/1096-911X(20010101)36:13.0.CO;2-0.Maris J.M., Guo C., Blake D., White P.S., Hogarty M.D., Thompson P.M., Rajalingam V., Gerbing R., Stram D.O., Matthay K.K., Seeger R.C., Brodeur G.M. Comprehensive analysis of chromosome 1p deletions in neuroblastoma. Med Pediatr Oncol 2001;36:32–6. doi: 10.1002/1096-911X(20010101)36:13.0.CO;2-0.White P.S., Thompson P.M., Seifried B.A., Sulman E.P., Jensen S.J., Guo C., Maris J.M., Hogarty M.D., Allen C., Biegel J.A., Matise T.C., Gregory S.G., Reynolds C.P., Brodeur G.M. Detailed molecular analysis of 1p36 in neuroblastoma. Med Pediatr Oncol 2001;36:37–41. doi: 10.1002/1096-911X(20010101)36:13.0.CO;2-L.White P.S., Thompson P.M., Seifried B.A., Sulman E.P., Jensen S.J., Guo C., Maris J.M., Hogarty M.D., Allen C., Biegel J.A., Matise T.C., Gregory S.G., Reynolds C.P., Brodeur G.M. Detailed molecular analysis of 1p36 in neuroblastoma. Med Pediatr Oncol 2001;36:37–41. doi: 10.1002/1096-911X(20010101)36:13.0.CO;2-L.Maris J.M., Kyemba S.M., Rebbeck T.R., White P.S., Sulman E.P., Jensen S.J., Allen C., Biegel J.A., Yanofsky R.A., Feldman G.L., Brodeur G.M. Familial predisposition to neuroblastoma does not map to chromosome band 1p36. Cancer Res 1996;56(15):3421–5. PMID: 8758905.Maris J.M., Kyemba S.M., Rebbeck T.R., White P.S., Sulman E.P., Jensen S.J., Allen C., Biegel J.A., Yanofsky R.A., Feldman G.L., Brodeur G.M. Familial predisposition to neuroblastoma does not map to chromosome band 1p36. Cancer Res 1996;56(15):3421–5. PMID: 8758905.Cohn S.L., Pearson A.D., London W.B., Monclair T., Ambros P.F., Brodeur G.M., Faldum A., Hero B., Iehara T., Machin D., Mosseri V., Simon T., Garaventa A., Castel V., Matthay K.K.; INRG Task Force. The International Neuroblastoma Risk Group (INRG) classification system: an INRG Task Force report. J Clin Oncol 2009;27(2):289–97. doi: 10.1200/JCO.2008.16.6785.Cohn S.L., Pearson A.D., London W.B., Monclair T., Ambros P.F., Brodeur G.M., Faldum A., Hero B., Iehara T., Machin D., Mosseri V., Simon T., Garaventa A., Castel V., Matthay K.K.; INRG Task Force. The International Neuroblastoma Risk Group (INRG) classification system: an INRG Task Force report. J Clin Oncol 2009;27(2):289–97. doi: 10.1200/JCO.2008.16.6785.Cunsolo C.L., Bicocchi M.P., Petti A.R., Tonini G.P. Numerical and structural aberrations in advanced neuroblastoma tumors by CGH analysis; survival correlates with chromosome 17 status. Br J Cancer 2000;83:1295–300. doi: 10.1054/bjoc.2000.1432.Cunsolo C.L., Bicocchi M.P., Petti A.R., Tonini G.P. Numerical and structural aberrations in advanced neuroblastoma tumors by CGH analysis; survival correlates with chromosome 17 status. Br J Cancer 2000;83:1295–300. doi: 10.1054/bjoc.2000.1432.Bown N. Neuroblastoma tumour genetics: clinical and biological aspects. J Clin Pathol 2001;54:897–910. PMID: 11729208.Bown N. Neuroblastoma tumour genetics: clinical and biological aspects. J Clin Pathol 2001;54:897–910. PMID: 11729208.Perri P., Longo L., Cusano R., McConville C.M., Rees S.A., Devoto M., Conte M., Ferrara G.B., Seri M., Romeo G., Tonini G.P. Weak linkage at 4p16 to predisposition for human neuroblastoma. Oncogene 2002;21:8356–60. doi: 10.1038/sj.onc.1206009.Perri P., Longo L., Cusano R., McConville C.M., Rees S.A., Devoto M., Conte M., Ferrara G.B., Seri M., Romeo G., Tonini G.P. Weak linkage at 4p16 to predisposition for human neuroblastoma. Oncogene 2002;21:8356–60. doi: 10.1038/sj.onc.1206009.Giordani L., Iolascon A., Servedio V., Mazzocco K., Longo L., Tonini G.P. Two regions of deletion in 9p22- p24 in neuroblastoma are frequently observed in favorable tumors. Cancer Genet Cytogenet 2002;135(1):42–7. doi: 10.1016/S0165-4608(01)00640-9.Giordani L., Iolascon A., Servedio V., Mazzocco K., Longo L., Tonini G.P. Two regions of deletion in 9p22- p24 in neuroblastoma are frequently observed in favorable tumors. Cancer Genet Cytogenet 2002;135(1):42–7. doi: 10.1016/S0165-4608(01)00640-9.Mosse Y., Greshock J., King A., Khazi D., Weber B.L., Maris J.M. Identification and high-resolution mapping of a constitutional 11q deletion in an infant with multifocal neuroblastoma. Lancet Oncol 2003;4(12):769–71. PMID: 14662434.Mosse Y., Greshock J., King A., Khazi D., Weber B.L., Maris J.M. Identification and high-resolution mapping of a constitutional 11q deletion in an infant with multifocal neuroblastoma. Lancet Oncol 2003;4(12):769–71. PMID: 14662434.Spitz R., Hero B., Ernestus K., Berthold F. Deletions in chromosome arms 3p and 11q are new prognostic markers in localized and 4s neuroblastoma. Clin Cancer Res 2003;9:52–8. PMID: 12538451.Spitz R., Hero B., Ernestus K., Berthold F. Deletions in chromosome arms 3p and 11q are new prognostic markers in localized and 4s neuroblastoma. Clin Cancer Res 2003;9:52–8. PMID: 12538451.Thompson P.M., Seifried B.A., Kyemba S.K., Jensen S.J., Guo C., Maris J.M., Brodeur G.M., Stram D.O., Seeger R.C., Gerbing R., Matthay K.K., Matise T.C., White P.S. Loss of heterozygosity for chromosome 14q in neuroblastoma. Med Pediatr Oncol 2001;36:28–31. doi: 10.1002/1096-911X(20010101)36:13.0.CO;2-0.Thompson P.M., Seifried B.A., Kyemba S.K., Jensen S.J., Guo C., Maris J.M., Brodeur G.M., Stram D.O., Seeger R.C., Gerbing R., Matthay K.K., Matise T.C., White P.S. Loss of heterozygosity for chromosome 14q in neuroblastoma. Med Pediatr Oncol 2001;36:28–31. doi: 10.1002/1096-911X(20010101)36:13.0.CO;2-0.Michels E., Vandesompele J., De Preter K., Hoebeeck J., Vermeulen J., Schramm A., Molenaar J.J., Menten B., Marques B., Stallings R.L., Combaret V., Devalck C., De Paepe A., Versteeg R., Eggert A., Laureys G., Van Roy N., Speleman F. Array CGH-based classification of neuroblastoma into genomic subgroups. Genes Chromosomes Cancer 2007;46(12):1098–108. doi: 10.1002/gcc.20496.Michels E., Vandesompele J., De Preter K., Hoebeeck J., Vermeulen J., Schramm A., Molenaar J.J., Menten B., Marques B., Stallings R.L., Combaret V., Devalck C., De Paepe A., Versteeg R., Eggert A., Laureys G., Van Roy N., Speleman F. Array CGH-based classification of neuroblastoma into genomic subgroups. Genes Chromosomes Cancer 2007;46(12):1098–108. doi: 10.1002/gcc.20496.Michels E., Vandesompele J., Hoebeeck J., Menten B., De Preter K., Laureys G., Van Roy N., Speleman F. Genome-wide measurement of DNA copy number changes in neuroblastoma: dissecting amplicons and mapping losses, gains and breakpoints. Cytogenet Genome Res 2006;115(3–4):273–82. doi: 10.1159/000095924.Michels E., Vandesompele J., Hoebeeck J., Menten B., De Preter K., Laureys G., Van Roy N., Speleman F. Genome-wide measurement of DNA copy number changes in neuroblastoma: dissecting amplicons and mapping losses, gains and breakpoints. Cytogenet Genome Res 2006;115(3–4):273–82. doi: 10.1159/000095924.Uryu K., Nishimura R., Kataoka K., Sato Y., Nakazawa A., Suzuki H., Yoshida K., Seki M., Hiwatari M., Isobe T., Shiraishi Y., Chiba K., Tanaka H., Miyano S., Koh K., Hanada R., Oka A., Hayashi Y., Ohira M., Kamijo T., Nagase H., Takimoto T., Tajiri T., Nakagawara A., Ogawa S., Takita J. Identification of the genetic and clinical characteristics of neuroblastomas using genome-wide analysis. Oncotarget 2017;8(64):107513–29. doi: 10.18632/oncotarget.22495.Uryu K., Nishimura R., Kataoka K., Sato Y., Nakazawa A., Suzuki H., Yoshida K., Seki M., Hiwatari M., Isobe T., Shiraishi Y., Chiba K., Tanaka H., Miyano S., Koh K., Hanada R., Oka A., Hayashi Y., Ohira M., Kamijo T., Nagase H., Takimoto T., Tajiri T., Nakagawara A., Ogawa S., Takita J. Identification of the genetic and clinical characteristics of neuroblastomas using genome-wide analysis. Oncotarget 2017;8(64):107513–29. doi: 10.18632/oncotarget.22495.Schleiermacher G., Mosseri V., London W.B., Maris J.M., Brodeur G.M., Attiyeh E., Haber M. , Khan J., Nakagawara A., Speleman F., Noguera R., Tonini G.P., Fischer M., Ambros I., Monclair T., Matthay K.K., Ambros P., Cohn, S.L., Pearson A.D.J. Segmental chromosomal alterations have prognostic impact in neuroblastoma: a report from the INRG project. Brit J Cancer 2012;107:1418–22.Schleiermacher G., Mosseri V., London W.B., Maris J.M., Brodeur G.M., Attiyeh E., Haber M. , Khan J., Nakagawara A., Speleman F., Noguera R., Tonini G.P., Fischer M., Ambros I., Monclair T., Matthay K.K., Ambros P., Cohn, S.L., Pearson A.D.J. Segmental chromosomal alterations have prognostic impact in neuroblastoma: a report from the INRG project. Brit J Cancer 2012;107:1418–22.doi: 10.1038/bjc.2012.375.doi: 10.1038/bjc.2012.375.Chen Q.R., Bilke S., Khan J. High-resolution cDNA microarray-based comparative genomic hybridization n analysis in neuroblastoma. Cancer Lett 2005;228:71–81. doi: 10.1016/j.canlet.2004.12.056.Chen Q.R., Bilke S., Khan J. High-resolution cDNA microarray-based comparative genomic hybridization n analysis in neuroblastoma. Cancer Lett 2005;228:71–81. doi: 10.1016/j.canlet.2004.12.056.Chen Q., Bilke S., Wei J.S., Whiteford C.C., Cenacchi N., Krasnoselsky A.L., Greer B.T., Chang-Gue S., Westermann F., Berthold F., Schwab M., Catchpoole D., Khan J. cDNA array-CGH profiling identifies genomic alterations specific to stage and MYCN-amplification in neuroblastoma. BMC Genomics 2004;5:70.Chen Q., Bilke S., Wei J.S., Whiteford C.C., Cenacchi N., Krasnoselsky A.L., Greer B.T., Chang-Gue S., Westermann F., Berthold F., Schwab M., Catchpoole D., Khan J. cDNA array-CGH profiling identifies genomic alterations specific to stage and MYCN-amplification in neuroblastoma. BMC Genomics 2004;5:70.doi: 10.1186/1471-2164-5-70.doi: 10.1186/1471-2164-5-70.Mosse Y.P., Diskin S.J., Wasserman N., Rinaldi K., Attiyeh E.F.,Mosse Y.P., Diskin S.J., Wasserman N., Rinaldi K., Attiyeh E.F.,Cole K., Jagannathan J., Bhambhani K., Winter C., Maris J.M. Neuroblastomas have distinct genomic DNA profiles that predict clinical phenotype and regional gene expression. Genes Chromosomes Cancer 2007;46(10):936–49. doi: 10.1002/gcc.20477.Cole K., Jagannathan J., Bhambhani K., Winter C., Maris J.M. Neuroblastomas have distinct genomic DNA profiles that predict clinical phenotype and regional gene expression. Genes Chromosomes Cancer 2007;46(10):936–49. doi: 10.1002/gcc.20477.

The authors declare that there are no conflicts of interest present.