title: ppGalNAc-T13: a new molecular marker of bone marrow involvement in neuroblastoma.
abstract: 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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: CNRS-UMR 8126, Interactions Moléculaires at Cancer, Villejuif, France.
authors.forename: Nora
authors.initials: N
authors.lastname: Berois
authors.forename: Etienne
authors.initials: E
authors.lastname: Blanc
authors.forename: Hugues
authors.initials: H
authors.lastname: Ripoche
authors.forename: Xénia
authors.initials: X
authors.lastname: Mergui
authors.forename: Felipe
authors.initials: F
authors.lastname: Trajtenberg
authors.forename: Sabrina
authors.initials: S
authors.lastname: Cantais
authors.forename: Michel
authors.initials: M
authors.lastname: Barrois
authors.forename: Philippe
authors.initials: P
authors.lastname: Dessen
authors.forename: Bertil
authors.initials: B
authors.lastname: Kågedal
authors.forename: Jean
authors.initials: J
authors.lastname: Bénard
authors.forename: Eduardo
authors.initials: E
authors.lastname: Osinaga
authors.forename: Gilda
authors.initials: G
authors.lastname: Raguénez
mesh_terms: D000293:Adolescent; D000328:Adult; D000818:Animals; D014408:Biomarkers, Tumor / Q000096:biosynthesis*; D019046:Bone Marrow Neoplasms / Q000175:diagnosis* / Q000378:metabolism / Q000556:secondary; D045744:Cell Line, Tumor; D002648:Child; D002675:Child, Preschool; D020869:Gene Expression Profiling; D006338:Heart Neoplasms / Q000175:diagnosis / Q000378:metabolism / Q000556:secondary; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D051379:Mice; D008819:Mice, Nude; D017350:N-Acetylgalactosaminyltransferases / Q000096:biosynthesis*; D009368:Neoplasm Transplantation; D009447:Neuroblastoma / Q000175:diagnosis* / Q000378:metabolism / Q000556:secondary; D012333:RNA, Messenger / Q000096:biosynthesis; D016019:Survival Analysis; D014183:Transplantation, Heterologous
chemical_list: D014408:Biomarkers, Tumor; D012333:RNA, Messenger; D017350:N-Acetylgalactosaminyltransferases; C470847:UDP-N-acetyl-alpha-D-galactosamine polypeptide N-acetylgalactosaminyltransferase 13, human