On the significance of germline cytogenetic rearrangements at MYCN locus in neuroblastoma

Molecular Cytogenetics

Janusz Limon¹  Elzbieta Adamkiewicz-Drozynska²  Ewa Izycka-Swieszewska³  Mariola Iliszko¹  Anna Ploszynska²  Jolanta Wierzba²  Magdalena Koczkowska¹  Beata S Lipska¹ 

[1] Department of Biology and Genetics, Medical University of Gdansk, Debinki 1str, 80211 Gdansk, Poland;Department of Pediatrics, Hematology and Oncology, Medical University of Gdansk, Debinki 7str, 80211 Gdansk, Poland;Laboratory of Pathology and Neuropathology, Debinki 1str, 80211 Gdansk, Poland

关键词: Partial 2p trisomy;    FRA2C;    MYCN;    Neuroblastoma;   

Others  :  1150771
DOI  :  10.1186/1755-8166-6-43

 received in 2013-07-19, accepted in 2013-09-20,  发布年份 2013

【 摘 要 】

Background

MYCN oncogene amplification is the most important prognostic factor in neuroblastoma. 25% neuroblastoma tumors have somatic amplifications at this locus but little is known about its constitutional aberrations and their potential role in carcinogenesis. Here, we have performed an array-CGH and qPCR characterization of two patients with constitutional partial 2p trisomy including MYCN genomic region.

Results

One of the patients had congenital neuroblastoma and showed presence of minute areas of gains and losses within the common fragile site FRA2C at 2p24 encompassing MYCN. The link between 2p24 germline rearrangements and neuroblastoma development was reassessed by reviewing similar cases in the literature.

Conclusions

It appears that constitutional rearrangements involving chromosome 2p24 may play role in NB development.

【 授权许可】

   
2013 Lipska et al.; licensee BioMed Central Ltd.

【 图 表 】

Figure 1.

Figure 2.

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【 参考文献 】

• [1]Schleiermacher G, Mosseri V, London WB, Maris JM, Brodeur GM, Attiyeh E, Haber M, Khan J, Nakagawara A, Speleman F, Noguera R, Tonini GP, Fischer M, Ambros I, Monclair T, Matthay KK, Ambros P, Cohn SL, Pearson AD: Segmental chromosomal alterations have prognostic impact in neuroblastoma: a report from the INRG project. Br J Cancer 2012, 107:1418-1422.
• [2]White PS, Thompson PM, Gotoh T, Okawa ER, Igarashi J, Kok M, Winter C, Gregory SG, Hogarty MD, Maris JM, Brodeur GM: Definition and characterization of a region of 1p36.3 consistently deleted in neuroblastoma. Oncogene 2005, 24:2684-2694.
• [3]Pugh TJ, Morozova O, Attiyeh EF, Asgharzadeh S, Wei JS, Auclair D, Carter SL, Cibulskis K, Hanna M, Kiezun A, Kim J, Lawrence MS, Lichenstein L, McKenna A, Pedamallu CS, Ramos AH, Shefler E, Sivachenko A, Sougnez C, Stewart C, Ally A, Birol I, Chiu R, Corbett RD, Hirst M, Jackman SD, Kamoh B, Khodabakshi AH, Krzywinski M, Lo A, et al.: The genetic landscape of high-risk neuroblastoma. Nat Genet 2013. doi: 10.1038/ng.2529
• [4]Janoueix-Lerosey I, Lequin D, Brugieres L, Ribeiro A, de Pontual L, Combaret V, Raynal V, Puisieux A, Schleiermacher G, Pierron G, Valteau-Couanet D, Frebourg T, Michon J, Lyonnet S, Amiel J, Delattre O: Somatic and germline activating mutations of the ALK kinase receptor in neuroblastoma. Nature 2008, 455:967-970.
• [5]Deyell RJ, Attiyeh EF: Advances in the understanding of constitutional and somatic genomic alterations in neuroblastoma. Cancer Genet 1988, 204:113-121.
• [6]Schwab M: MYCN in neuronal tumours. Cancer Lett 2004, 204:179-187.
• [7]Feenstra I, Fang J, Koolen DA, Siezen A, Evans C, Winter RM, Lees MM, Riegel M, de Vries BB, Van Ravenswaaij CM, Schinzel A: European Cytogeneticists Association Register of Unbalanced Chromosome Aberrations (ECARUCA); an online database for rare chromosome abnormalities. Eur J Med Genet 2006, 49:279-291.
• [8]Firth HV, Richards SM, Bevan AP, Clayton S, Corpas M, Rajan D, Van Vooren S, Moreau Y, Pettett RM, Carter NP DECIPHER: Database of chromosomal imbalance and phenotype in humans using ensembl resources. Am J Hum Genet 2009, 84:524-533.
• [9]van Mater D, Knelson EH, Kaiser-Rogers KA, Armstrong MB: Neuroblastoma in a pediatric patient with a microduplication of 2p involving the MYCN locus. Am J Med Genet 2013, 161:605-610.
• [10]Cohn SL, Pearson AD, London WB, Monclair T, Ambros PF, Brodeur GM, Faldum A, Hero B, Iehara T, Machin D, Mosseri V, Simon T, Garaventa A, Castel V, Matthay KK, INRG Task Force: The International Neuroblastoma Risk Group (INRG) classification system: an INRG Task Force report. J Clin Oncol 2009, 10:289-297.
• [11]Nagano H, Kano Y, Kobuchi S, Kajitani T: A case of partial 2p trisomy with neuroblastoma. Jinrui Idengaku Zasshi 1980, 25:39-45.
• [12]Patel JS, Pearson J, Willatt L, Andrews T, Beach R, Green A: Germline duplication of chromosome 2p and neuroblastoma. J Med Genet 1997, 34:949-951.
• [13]Yuksel A, Seven M, Karaman B, Yilmaz S, Deviren A, Hacihanefioglu S, Basaran S: Neuroblastoma in a dysmorphic girl with a partial duplication of 2p caused by an unbalanced translocation. Clin Dysmorphol 2002, 11:39-42.
• [14]Soh SY, Stavropoulos D, Bowdin S, Thorner P, Baruchel S, Malkin D, Meyn MS, Irwin M: Metachronous neuroblastoma in an infant with constitutional unbalanced translocation t(2;16)(p23; p13.3) involving ALK. Poster presentation at ANR Stockholm 2010. POC38
• [15]Dowa Y, Yamamoto T, Abe Y, Kobayashi M, Hoshino R, Tanaka K, Aida N, Take H, Kato K, Tanaka Y, Ariyama J, Harada N, Matsumoto N, Kurosawa K: Congenital neuroblastoma in a patient with partial trisomy of 2p. J Pediatr Hematol Oncol 2006, 28:379-382.
• [16]Liu P, Carvalho CMB, Hastings PJ, Lupski JR: Mechanisms for recurrent and complex human genomic rearrangements. Curr Opin Genet Dev 2012, 22:211-220.
• [17]Forment JV, Kaidi A, Jackson SP: Chromothripsis and cancer: causes and consequence of chromosome shattering. Nature Rev Cancer 2012, 12:663-670.
• [18]Kloosterman WP, Tavakoli-Yaraki M, van Roosmalen MJ, van Binsbergen E, Renkens I, Duran K, Ballarati L, Vergult S, Giardino D, Hansson K, Ruivenkamp CA, Jager M, van Haeringen A, Ippel EF, Haaf T, Passarge E, Hochstenbach R, Menten B, Larizza L, Guryev V, Poot M, Cuppen E: Constitutional chromothripsis rearrangements involve clustered double-stranded DNA breaks and nonhomologous repair mechanisms. Cell Rep 2012, 1:648-655.
• [19]Molenaar JJ, Koster J, Zwijnenburg DA, van Sluis P, Valentijn LJ, van der Ploeg I, Hamdi M, van Nes J, Westerman BA, van Arkel J, Ebus ME, Haneveld F, Lakeman A, Schild L, Molenaar P, Stroeken P, van Noesel MM, Ora I, Santo EE, Caron HN, Westerhout EM, Versteeg R: Sequencing of neuroblastoma identifies chromothripsis and defects in neuritogenesis genes. Nature 2012, 483:589-593.
• [20]Storlazzi CT, Lonoce A, Guastadisegni MC, Trombetta D, D'Addabbo P, Daniele G, L'Abbate A, Macchia G, Surace C, Kok K, Ullmann R, Purgato S, Palumbo O, Carella M, Ambros PF, Rocchi M: Gene amplification as double minutes or homogeneously staining regions in solid tumors: origin and structure. Genome Res 2010, 20:1198-1206.
• [21]Blumrich A, Zapatka M, Brueckner LM, Zheglo D, Schwab M, Savelyeva L: The FRA2C common fragile site maps to the borders of MYCN amplicons in neuroblastoma and is associated with gross chromosomal rearrangements in different cancers. Hum Mol Genet 2011, 20:1488-1501.
• [22]Yunis JJ, Soreng A: Constiutive fragile sites and cancer. Science 1984, 226:1199-1204.
• [23]Schwartz M, Zlotorynski E, Kerem B: The molecular basis of common and rare fragile sites. Cancer Lett 2005, 232:13-26.
• [24]Miller SA, Dykes DD, Polesky HF: A simple salting out procedure for extracting DNA from human nucleated cells. Nucleic Acids Res 1988, 16:1215.