Cancers (Dec 2022)

GD2 Expression in Medulloblastoma and Neuroblastoma for Personalized Immunotherapy: A Matter of Subtype

  • Claudia Paret,
  • Arsenij Ustjanzew,
  • Sara Ersali,
  • Larissa Seidmann,
  • Richard Jennemann,
  • Nicole Ziegler,
  • Khalifa El Malki,
  • Alexandra Russo,
  • Arthur Wingerter,
  • Franziska Ortmüller,
  • Angelina Bornas,
  • Pia Charlotte Wehling,
  • Adina Lepădatu,
  • Malte Ottenhausen,
  • Wilfried Roth,
  • Clemens Sommer,
  • Barbara Fliss,
  • Katrin B. M. Frauenknecht,
  • Roger Sandhoff,
  • Jörg Faber

DOI
https://doi.org/10.3390/cancers14246051
Journal volume & issue
Vol. 14, no. 24
p. 6051

Abstract

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Neuroblastoma (NBL) and medulloblastoma (MB) are aggressive pediatric cancers which can benefit from therapies targeting gangliosides. Therefore, we compared the ganglioside profile of 9 MB and 14 NBL samples by thin layer chromatography and mass spectrometry. NBL had the highest expression of GD2 (median 0.54 nmol GD2/mg protein), and also expressed complex gangliosides. GD2-low samples expressed GD1a and were more differentiated. MB mainly expressed GD2 (median 0.032 nmol GD2/mg protein) or GM3. Four sonic hedgehog-activated (SHH) as well as one group 4 and one group 3 MBs were GD2-positive. Two group 3 MB samples were GD2-negative but GM3-positive. N-glycolyl neuraminic acid-containing GM3 was neither detected in NBL nor MB by mass spectrometry. Furthermore, a GD2-phenotype predicting two-gene signature (ST8SIA1 and B4GALNT1) was applied to RNA-Seq datasets, including 86 MBs and validated by qRT-PCR. The signature values were decreased in group 3 and wingless-activated (WNT) compared to SHH and group 4 MBs. These results suggest that while NBL is GD2-positive, only some MB patients can benefit from a GD2-directed therapy. The expression of genes involved in the ganglioside synthesis may allow the identification of GD2-positive MBs. Finally, the ganglioside profile may reflect the differentiation status in NBL and could help to define MB subtypes.

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