GD2 synthase: a new molecular marker for detecting neuroblastoma.
BACKGROUND
Neuroblastomas (NBs) almost ubiquitously express the ganglioside GD2. GD2 synthesis is dependent on the key enzyme GD2 synthase. Thus, GD2 synthase transcript may prove to be a potential molecular marker of NB.


METHODS
Seventy-seven NB tumor tissues of all stages, 5 NB cell lines, and 26 normal bone marrows (BMs) and peripheral blood (PBL) samples, as well as 26 non-NB remission-BMs were analyzed for the expression of GD2 synthase by a highly sensitive reverse transcriptase-polymerase chain reaction (RT-PCR) and chemiluminescence detection. One hundred fifty-two NB BMs were tested and comparisons were made among three independent detection techniques, namely GD2 synthase RT-PCR, immunofluorescence (IF), and histology (HIST).


RESULTS
GD2 synthase transcript was present in 5 of 5 cell lines and in 77 of 77 tumors tested. Among 116 marrows that were positive by at least 1 of the 3 methods, 78% were detectable by GD2 synthase, 68% by IF, and 46% by HIST. Seventy-six percent of positive BMs that were obtained during treatment and follow-up had GD2 synthase expression, whereas only 29% were HIST positive. Correlation between RT-PCR and IF was high (P = 0.001), and positivity by 3 out of 3 methods was strongly correlated with poor survival (P < 0.01). Of note, marrows tested at the time of chemotherapy were positive by at least 2 out of 3 methods and were associated with adverse outcome (P = 0.01). Serial samples (n = 28) in 5 patients demonstrated close agreement between RT-PCR and patient disease status.


CONCLUSIONS
The current study found that molecular detection of GD2 synthase transcript in NB BMs may have potential value in detecting rare tumor cells.
Lo Piccolo
M S
MS
Department of Pediatrics, Memorial Sloan-Kettering Cancer Center, 1275 York Avenue, New York, NY 10021, USA.
Cheung
N K
NK
Cheung
I Y
IY
D014408:Biomarkers, Tumor / Q000378:metabolism*; D001853:Bone Marrow / Q000201:enzymology; D005455:Fluorescent Antibody Technique; D006801:Humans; D008163:Luminescent Measurements; D017350:N-Acetylgalactosaminyltransferases / Q000235:genetics / Q000378:metabolism*; D009367:Neoplasm Staging; D009447:Neuroblastoma / Q000175:diagnosis / Q000201:enzymology* / Q000473:pathology; D012313:RNA / Q000032:analysis; D012189:Retrospective Studies; D020133:Reverse Transcriptase Polymerase Chain Reaction; D016019:Survival Analysis; D014407:Tumor Cells, Cultured
D014408:Biomarkers, Tumor; D012313:RNA; D017350:N-Acetylgalactosaminyltransferases; C023220:(N-acetylneuraminyl)-galactosylglucosylceramide N-acetylgalactosaminyltransferase