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High-risk neuroblastoma tumors with 11q-deletion display a poor prognostic, chromosome instability phenotype with later onset.

Journal article
Authors Helena Carén
Hanna Kryh
Maria Nethander
Rose-Marie Sjöberg
Catarina Träger
Staffan Nilsson
Jonas Abrahamsson
Per Kogner
Tommy Martinsson
Published in PNAS
Volume 107
Issue 9
Pages 4323-4328
ISSN 1091-6490
Publication year 2010
Published at Institute of Biomedicine, Department of Medical and Clinical Genetics
Department of Mathematical Sciences, Mathematical Statistics
Pages 4323-4328
Language en
Links dx.doi.org/10.1073/pnas.0910684107
Keywords comparative genomic hybridization/SNP array chromosomal aberration, H2AFX, MYCN amplification, pediatric tumor
Subject categories Medical and Health Sciences

Abstract

Analysis of chromosomal aberrations is used to determine the prognosis of neuroblastomas (NBs) and to aid treatment decisions. MYCN amplification (MNA) alone is an incomplete poor prognostic factor, and chromosome 11q status has recently been included in risk classification. We analyzed 165 NB tumors using high-density SNP microarrays and specifically compared the high-risk groups defined by MNA (n = 37) and 11q-deletion (n = 21). Median patient age at diagnosis was 21 months for MNA tumors and 42 months for 11q-deletion tumors, and median survival time after diagnosis was 16 months for MNA and 40 months for 11q deletion. Overall survival (at 8 years) was approximately 35% in both groups. MNA and 11q deletion were almost mutually exclusive; only one case harbored both aberrations. The numbers of segmental aberrations differed significantly; the MNA group had a median of four aberrations, whereas the 11q-deletion group had 12. The high frequency of chromosomal breaks in the 11q-deletion group is suggestive of a chromosomal instability phenotype gene located in 11q; one such gene, H2AFX, is located in 11q23.3 (within the 11q-deletion region). Furthermore, in the groups with segmental aberrations without MNA or 11q deletion, the tumors with 17q gain have worse prognosis than those with segmental aberrations without 17q gain, which have a favorable outcome. This study has implications for therapy in different risk groups and stresses that genome-wide microarray analyses should be included in clinical management to fully evaluate risk, aid diagnosis, and guide treatment.

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