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@ARTICLE{Paret:304578,
author = {C. Paret$^*$ and A. Wingerter and L. Seidmann and A.
Ustjanzew and S. Sathyamurthy$^*$ and J. Ludwig$^*$ and P.
Schwickerath$^*$ and C. Brignole and F. Pastorino and S.
Wagner and K. El Malki and W. Roth and R. Sandhoff$^*$ and
J. Faber$^*$},
title = {{G}anglioside {P}rofiling {U}ncovers {D}istinct {P}atterns
in {H}igh-{R}isk {N}euroblastoma.},
journal = {International journal of molecular sciences},
volume = {26},
number = {17},
issn = {1422-0067},
address = {Basel},
publisher = {Molecular Diversity Preservation International},
reportid = {DKFZ-2025-01901},
pages = {8431},
year = {2025},
note = {#LA:A411#},
abstract = {High-risk (HR) neuroblastoma (NBL) patients often receive
standardized treatment despite wide variations in clinical
outcomes, underscoring the need for improved stratification
tools. A distinguishing feature of NBL is the
patient-specific expression of gangliosides (GGs),
particularly GD2, which may serve as biomarkers. We analyzed
GG profiles in 18 patient-derived tumors and 11 NBL cell
lines using thin-layer chromatography and mass spectrometry.
Expression of 0-, a-, and b-series GGs was examined and
correlated with clinical risk, outcome, and gene expression
data. Low-risk (LR) tumors expressed higher levels of
complex b-series GGs. In HR tumors, five GG profiles (A-E)
were identified. Profile A featured complex b-series GGs; B
showed GD2 dominance; C showed synthesis arrest at GM3 or
GD3 due to low expression of the GM2/GD2 synthase, encoded
by the B4GALNT1 gene; D included complex a- and b-series
GGs; and E was marked by GM2 and GD1a prevalence. B4GALNT1
expression served as a prognostic marker. Relapsed tumors
following anti-GD2 therapy typically exhibited reduced GD2
levels, except for one profile A tumor that displayed a
ceramide anchor shorter than those found in LR tumors.
Astonishingly, the ceramide anchor composition of GD2 itself
appears to separate LR and HR NBL, hinting at a role of
ceramide synthases in NBL biology. All cell lines expressed
GM2, but exhibited very low levels of complex b-series GGs.
Profile C was found only in cell lines of the mesenchymal
subtype. These findings support further investigation of GG
composition and associated enzyme expression as potential
biomarkers for risk stratification and treatment response in
NBL.},
keywords = {B4GALNT1 (Other) / GD2 (Other) / ceramide (Other) /
dinutuximab (Other) / gangliosides (Other) / naxitamab
(Other) / neuroblastoma (Other)},
cin = {FM01 / A411},
ddc = {540},
cid = {I:(DE-He78)FM01-20160331 / I:(DE-He78)A411-20160331},
pnm = {311 - Zellbiologie und Tumorbiologie (POF4-311)},
pid = {G:(DE-HGF)POF4-311},
typ = {PUB:(DE-HGF)16},
pubmed = {pmid:40943355},
pmc = {pmc:PMC12428964},
doi = {10.3390/ijms26178431},
url = {https://inrepo02.dkfz.de/record/304578},
}