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Clinical Chemistry 52: 1701-1712, 2006. First published July 27, 2006; 10.1373/clinchem.2006.067975
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(Clinical Chemistry. 2006;52:1701-1712.)
© 2006 American Association for Clinical Chemistry, Inc.

Cancer Diagnostics

ppGalNAc-T13: A New Molecular Marker of Bone Marrow Involvement in Neuroblastoma

Nora Berois4,3, Etienne Blanc1,3, Hugues Ripoche2, Xénia Mergui1, Felipe Trajtenberg4, Sabrina Cantais1, Michel Barrois3, Philippe Dessen2, Bertil Kågedal5, Jean Bénard1,3, Eduardo Osinaga4 and Gilda Raguénez1,a

1 CNRS-UMR 8126, Interactions Moléculaires at Cancer; 2 CNRS–FRE 2939, Groupe de Bioinformatique; and 3 Département de Biologie et Pathologie Médicales, IFR54 Institut Gustave Roussy, Villejuif, France.
4 Departamento de Bioquímica, Laboratorio de Oncologia Basica, Facultad de Medicina, Universidad de la República, Avda. Montevideo, Uruguay.
5 University of Linköping, Faculty of Health Sciences, Division of Clinical Chemistry, Sweden.

aAddress correspondence to this author at: CNRS-UMR 8126, Interactions Moléculaires et Cancer, IFR54 Institut Gustave Roussy, 39, rue Camille Desmoulins, 94805 Villejuif, France. E-mail raguenez{at}igr.fr.

Background: To identify new molecular markers of bone marrow dissemination in human neuroblastoma (NB), we studied the transcriptome profiles of malignant neuroblasts established from the human MYCN-amplified IGR-N-91 model.

Methods: This experimental model includes human neuroblastoma cells derived from a subcutaneous stage 4 disease, myocardium (Myoc) and bone marrow (BM) metastatic cells.

Results: Gene expression profiles obtained with Agilent oligo microarrays revealed a set of 107 differentially expressed genes in the metastatic neuroblasts. This set included up-regulated genes involved in chemoresistance, cell motility, neuronal structure/signaling, and the recently characterized GALNT13 gene encoding a glycosyltransferase that initiates mucin-type O-glycosylation. Because the glycosylation process is involved in the progression of primary tumor to metastatic disease, we investigated whether the most strongly up-regulated gene, GALNT13, might be a marker of bone marrow involvement in stage 4 NB patients. Importantly, in the BM of healthy adults no GALNT13 transcript was detected with analysis by quantitative (n = 3) and nested reverse transcription-PCR (n = 4) assays. In contrast, GALNT13 transcripts were detected in 23/23 cytologically involved BM samples obtained at diagnosis of stage 4 NB patients and in 5/27 cytologically noninvolved BM samples obtained from patients with stage 1–4 and 4S and treated stage 4 NB. The quantitative measurements of tyrosine hydroxylase (TH), ganglioside D2 synthase, dopa decarboxylase, and GALNT13 transcript values were compared in the same NB patients, and the results showed that GALNT13 expression was most highly correlated to poor clinical outcome at diagnosis.

Conclusion: We propose ppGalNAc-T13 as a new informative marker for the molecular diagnosis of BM involvement and the follow-up of minimal residual disease in NB patients.






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