Received on February 1, 2006
Accepted on June 21, 2006

Cancer Diagnostics

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

¹ Departamento de Bioquímica, Laboratorio de Oncologia Basica, Facultad de Medicina, Universidad de la República, Avda. Montevideo, Uruguay
² CNRS-UMR 8126, Interactions Moléculaires at Cancer, IFR54 Institut Gustave Roussy, Villejuif, France
³ CNRS\NFRE 2939, Groupe de Bioinformatique, IFR54 Institut Gustave Roussy, Villejuif, France
⁴ Département de Biologie et Pathologie Médicales, IFR54 Institut Gustave Roussy, Villejuif, France
⁵ University of Linköping, Faculty of Health Sciences, Division of Clinical Chemistry, Sweden
⁶ CNRS-UMR 8126, Interactions Moléculaires at Cancer, IFR54 Institut Gustave Roussy, Villejuif, France, and Département de Biologie et Pathologie Médicales, IFR54 Institut Gustave Roussy, Villejuif, France

^* To whom correspondence should be addressed. 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 primary tumor xenograft (PTX), myocardium (Myoc) and bone marrow (BM) metastatic cells.

Results: Gene expression profiles using 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, no GALNT13 transcript was detected in the BM of healthy adults when analyzed 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 patients and in 5/27 cytologically noninvolved BM obtained from stage 1-4 and 4S, as well as treated stage 4 NB patients. The quantitative measurements of tyrosine hydroxylase (TH), GD₂ synthase, DDC, and GALNT13 transcript values were compared in the same NB patients, and the results showed that GALNT13 expression was the best marker to be correlated to poor clinical outcome at diagnosis.

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