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Determination of 17q gain in patients with neuroblastoma by analysis of circulating DNA
Author(s) -
Combaret Valérie,
Bréjon Stéphanie,
Iacono Isabelle,
Schleiermacher Gudrun,
Pierron Gäelle,
Ribeiro Agnès,
Bergeron Christophe,
Marabelle Aurélien,
Puisieux Alain
Publication year - 2011
Publication title -
pediatric blood and cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.116
H-Index - 105
eISSN - 1545-5017
pISSN - 1545-5009
DOI - 10.1002/pbc.22816
Subject(s) - multiplex ligation dependent probe amplification , comparative genomic hybridization , multiplex , medicine , neuroblastoma , genomic dna , chromosome , survivin , isochromosome , microbiology and biotechnology , cancer research , dna , cancer , oncology , pathology , gene , biology , genetics , karyotype , exon , cell culture
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. Pediatr Blood Cancer 2011;56:757–761. © 2011 Wiley‐Liss, Inc.