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Pediatr Blood Cancer. 2011 May;56(5):757-61. doi: 10.1002/pbc.22816. Epub 2011 Jan 11.

Determination of 17q gain in patients with neuroblastoma by analysis of circulating DNA.

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  • 1Centre Léon Bérard, Laboratoire de Recherche Translationnelle, Lyon Cedex, France. combaret@lyon.fnclcc.fr

Abstract

BACKGROUND:

Retrospective studies have demonstrated the prognostic impact of genomic profiles in neuroblastoma (NB). Segmental chromosome alterations have been found useful for identifying tumors with a high risk of relapse. As the gain of chromosome arm 17q is the most frequent chromosome alteration reported in NB primary tumors, we evaluated the presence of this 17q gain in the peripheral blood of patients with NB.

PROCEDURE:

Using duplex quantitative real-time PCR, we quantified simultaneously MPO (17q.23.1) and a reference gene, p53, and Survivin (17q25) and p53. MPO and Survivin copy numbers were evaluated as MPO/p53 and Survivin/p53 ratios in 142 serum or plasma samples in which 17q status had been determined by array-based comparative genomic hybridization (aCGH) or multiplex ligation-dependent probe amplification (MLPA).

RESULTS:

In patients <18 months of age, serum-based determination of 17q gain in DNA sequences had good specificity (94.4%) and 58.8% sensitivity (P < 0.001). In contrast, for patients over 18 months of age, the approach exhibited moderate specificity (71.4%) and 51.2% sensitivity (P = ns). Similar results were observed in patients with tumors without MYCN amplification.

CONCLUSION:

Our results show that 17q gain determination in circulating DNA is possible and suggest that this non-invasive test could be useful for very young children when no reliable information on genomic alterations is obtained by aCGH or MPLA analysis of tumor samples This test is complementary to previously developed techniques for detecting circulating MYCN DNA sequences.

Copyright © 2011 Wiley-Liss, Inc.

PMID:
21370407
[PubMed - indexed for MEDLINE]
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