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Gene expression profiling of 1p35–36 genes in neuroblastoma

Oncogene volume 23, pages 5912–5922 (2004)Cite this article

Abstract

Deletion of the chromosome 1p36 region is a frequent abnormality in neuroblastoma. To gain further insights into the role of this alteration in oncogenesis, we have constructed a specific cDNA microarray representing most known genes and ESTs from the 1p35–36 region and analysed the expression profiles of 15 neuroblastoma cell lines and 28 neuroblastoma tumours. Hierarchical clustering using expression levels of 320 cDNAs from 1p35–36 separated localized or 4S cases without 1p deletion from advanced stages and cell lines. Supervised learning classification enabled to predict reliably the status of chromosome 1p according to its expression profile. Around 15% of the genes or ESTs presented a significantly decreased expression in samples with 1p deletion as compared to 1p-normal samples suggesting that 1p deletion results in a gene dosage effect on a subset of genes critical for the development of 1p-deleted neuroblastoma. Several genes presumed to have functions in neural differentiation (CDC42, VAMP3, CLSTN1), signal transduction in neural cells (GNB1) and cell cycle regulation (STMN1, RPA2, RBAF600, FBXO6, MAD2L2) exhibited a decreased expression in samples presenting 1p deletion. The identification of such genes provides baseline information for further studies to elucidate how these genes could individually or collectively play a critical role in neuroblastoma tumorigenesis.

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Acknowledgements

We thank V Combaret and R Versteeg for providing cell lines used in this work. We also thank Angélique Joannot for technical help with Q-RT–PCR and Stéphane Liva for bio-informatic analysis. We thank F Mechinaud, J Michon, H Rubie, D Sommelet and P Tron for clinical information on the patients. This work was supported by grants from the Comité de Paris of the Ligue Nationale Contre le Cancer (Associated Laboratory) and from the Association pour la Recherche contre le Cancer.

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Authors and Affiliations

  1. INSERM U509, Laboratoire de Pathologie Moléculaire des Cancers, Institut Curie – Section de Recherche, Pavillon Trouillet-Rossignol 26, rue d’Ulm, Paris, Cedex 05, 75248, France

    Isabelle Janoueix-Lerosey, Eugene Novikov, Marta Monteiro, Nadège Gruel, Gudrun Schleiermacher & Olivier Delattre

  2. Equipe TAGC, Centre d’Immunologie de Marseille-Luminy, Case 906, Marseille, Cedex 09, 13288, France

    Béatrice Loriod & Catherine Nguyen

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  1. Isabelle Janoueix-Lerosey
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  2. Eugene Novikov
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Correspondence to Olivier Delattre.

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Supplementary information accompanies the paper on Oncogene website (http://www.nature.com/onc).

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Janoueix-Lerosey, I., Novikov, E., Monteiro, M. et al. Gene expression profiling of 1p35–36 genes in neuroblastoma. Oncogene 23, 5912–5922 (2004). https://doi.org/10.1038/sj.onc.1207784

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