Oligonucleotide array-based comparative genomic hybridization (aCGH) of 90 neuroblastomas reveals aberration patterns closely associated with relapse pattern and outcome

被引:63
作者
Spitz, Ruediger
Oberthuer, Andre
Zapatka, Marc
Brors, Benedikt
Hero, Barbara
Ernestus, Karen
Oestreich, Joern
Fischer, Matthias
Simon, Thorsten
Berthold, Frank
机构
[1] Univ Cologne, Childrens Hosp, Dept Paediat Oncol & Haematol, D-50924 Cologne, Germany
[2] Deutsch Krebsforschungszentrum, DKFZ, Dept Theoret Bioinformat, D-6900 Heidelberg, Germany
[3] Univ Cologne, Inst Pathol, D-50924 Cologne, Germany
[4] Ctr Mol Med Cologne, Cologne, Germany
关键词
D O I
10.1002/gcc.20376
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
The study of genomic alterations in neuroblastoma is of particular importance since several cytogenetic markers proved to be closely associated with the clinical phenotype. To disclose patterns of gains and losses, we performed high-resolution oligonucleotide array-based comparative genomic hybridization (aCGH). A total cohort of 90 patients was classified into 6 subsets according to tumor stage and outcome: Stages 1-3+ (with event), Stage 1-3- (no event), Stage 4+/-, and Stage 4S+/-. The aberration patterns in Stages 1-3- and 4S- tumors differed from all other groups as they were predominantly characterized by losses (3, 4, 14, X) and gains (7, 17) of whole chromosomes. However, 59/65 (91%) tumors of Stages 1-3+ or Stage 4 revealed numerous structural copy number alterations (sCNA). While deletions in chromosomes 1, 3, and I I discriminated outcome in Stage 4, there were no specific sCNA that distinguished tumor stage within the subgroup of unfavorable tumors. sCNA in 1p, 3p, 11q, 17q, or MYCN amplification (MNA) was seen among 22/24 patients who died, 10/12 with metastatic relapses, and 5/9 with local recurrences. Detailed breakpoint analyses on chromosomes 1, 3, 11, and 17 disclosed preferred breaking areas, although breakpoints were not identical. Amplifications were found in 18 patients and involved 2p24 (MYCN) and other segments of chromosome 2, as well as regions on chromosome arms 6q, 12q, and 17q. One single feature in 21q21.1 (BU678720, without known function yet) attracted particular attention since five patients showed a homozygous loss of this sequence. This article contains Supplementary Material available at http://www.interscience.wiley.com/jpages/1045-2257/suppmat. (c) 2006 Wiley-Liss, Inc.
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页码:1130 / 1142
页数:13
相关论文
共 37 条
  • [1] Chromosome 1p and 11q deletions and outcome in neuroblastoma
    Attiyeh, EF
    London, WB
    Mossé, YP
    Wang, Q
    Winter, C
    Khazi, D
    McGrady, PW
    Seeger, RC
    Look, AT
    Shimada, H
    Brodeur, GM
    Cohn, SL
    Matthay, KK
    Maris, JM
    [J]. NEW ENGLAND JOURNAL OF MEDICINE, 2005, 353 (21) : 2243 - 2253
  • [2] Comparative genomic hybridization using oligonucleotide microarrays and total genomic DNA
    Barrett, MT
    Scheffer, A
    Ben-Dor, A
    Sampas, N
    Lipson, D
    Kincaid, R
    Tsang, P
    Curry, B
    Baird, K
    Meltzer, PS
    Yakhini, Z
    Bruhn, L
    Laderman, S
    [J]. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2004, 101 (51) : 17765 - 17770
  • [3] Chromosomal localization of DNA amplifications in neuroblastoma tumors using cDNA microarray comparative genomic hybridization
    Beheshti, B
    Braude, I
    Marrano, P
    Thorner, P
    Zielenska, M
    Squire, JA
    [J]. NEOPLASIA, 2003, 5 (01): : 53 - 62
  • [4] Inferring a tumor progression model for neuroblastoma from genomic data
    Bilke, S
    Chen, QR
    Westerman, F
    Schwab, M
    Catchpoole, D
    Khan, J
    [J]. JOURNAL OF CLINICAL ONCOLOGY, 2005, 23 (29) : 7322 - 7331
  • [5] Brinkschmidt C, 1997, J PATHOL, V181, P394
  • [6] REVISIONS OF THE INTERNATIONAL CRITERIA FOR NEUROBLASTOMA DIAGNOSIS, STAGING, AND RESPONSE TO TREATMENT
    BRODEUR, GM
    PRITCHARD, J
    BERTHOLD, F
    CARLSEN, NLT
    CASTEL, V
    CASTLEBERRY, RP
    DEBERNARDI, B
    EVANS, AE
    FAVROT, M
    HEDBORG, F
    KANEKO, M
    KEMSHEAD, J
    LAMPERT, F
    LEE, REJ
    LOOK, AT
    PEARSON, ADJ
    PHILIP, T
    ROALD, B
    SAWADA, T
    SEEGER, RC
    TSUCHIDA, Y
    VOUTE, PA
    [J]. JOURNAL OF CLINICAL ONCOLOGY, 1993, 11 (08) : 1466 - 1477
  • [7] CDNA array-CGH profiling identifies genomic alterations specific to stage and MYCN-amplification in neuroblastoma -: art. no. 70
    Chen, QR
    Bilke, S
    Wei, JS
    Whiteford, CC
    Cenacchi, N
    Krasnoselsky, AL
    Greer, BT
    Son, CG
    Westermann, F
    Berthold, F
    Schwab, M
    Catchpoole, D
    Khan, J
    [J]. BMC GENOMICS, 2004, 5 (1)
  • [8] Quantification of MYCN, DDX1, and NAG gene copy number in neuroblastoma using a real-time quantitative PCR assay
    De Preter, K
    Speleman, F
    Combaret, V
    Lunec, J
    Laureys, G
    Eussen, BHJ
    Francotte, N
    Board, J
    Pearson, ADJ
    De Paepe, A
    Van Roy, N
    Vandesompele, J
    [J]. MODERN PATHOLOGY, 2002, 15 (02) : 159 - 166
  • [9] Positional and functional mapping of a neuroblastoma differentiation gene on chromosome 11 -: art. no. 97
    De Preter, K
    Vandesompele, J
    Menten, B
    Carr, P
    Fiegler, H
    Edsjö, A
    Carter, NP
    Yigit, N
    Waelput, W
    Van Roy, N
    Bader, S
    Påhlman, S
    Speleman, F
    [J]. BMC GENOMICS, 2005, 6 (1)
  • [10] Allelic deletion at 11q23 is common in MYCN single copy neuroblastomas
    Guo, C
    White, PS
    Weiss, MJ
    Hogarty, MD
    Thompson, PM
    Stram, DO
    Gerbing, R
    Matthay, KK
    Seeger, RC
    Brodeur, GM
    Maris, JM
    [J]. ONCOGENE, 1999, 18 (35) : 4948 - 4957