ppGalNAc-T13: a new molecular marker of bone marrow involvement in neuroblastoma.
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.
Berois
Nora
N
CNRS-UMR 8126, Interactions Moléculaires at Cancer, Villejuif, France.
Blanc
Etienne
E
Ripoche
Hugues
H
Mergui
Xénia
X
Trajtenberg
Felipe
F
Cantais
Sabrina
S
Barrois
Michel
M
Dessen
Philippe
P
Kågedal
Bertil
B
Bénard
Jean
J
Osinaga
Eduardo
E
Raguénez
Gilda
G
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
D014408:Biomarkers, Tumor; D012333:RNA, Messenger; D017350:N-Acetylgalactosaminyltransferases; C470847:UDP-N-acetyl-alpha-D-galactosamine polypeptide N-acetylgalactosaminyltransferase 13, human