Background: G_D2 is a ganglioside that is ubiquitously expressed in the plasma membrane of neuroblastoma

and is shed into the circulation.

Procedure: G_D2 was measured with a high-pressure liquid chromatography/tandem mass spectrometry

assay in serum or plasma from 40 children without cancer (controls) and in biobanked

samples from 128 (73 high-risk) children with neuroblastic tumors at diagnosis, 56 children with

relapsed neuroblastoma, 14 children with high-risk neuroblastoma after treatment, and 8 to 12

children each with 10 other common childhood cancers at diagnosis.

Results: The C₁₈ (18 carbon fatty acid) lipoform was the predominant circulating form of

G_D2 in controls and in patients with neuroblastoma. The median concentration of G_D2 in children

with high-risk neuroblastoma at diagnosis was 167 nM (range, 16.1-1060 nM), which was

30-fold higher than the median concentration (5.6 nM) in controls. G_D2 was not elevated in

serum from children with the differentiated neuroblastic tumors, ganglioneuroma (n = 10) and

ganglioneuroblastoma-intermixed subtype (n = 12), and in children with 10 other childhood cancers.

G_D2 concentrations were significantly higher in serum from children with MYCN-amplified

tumors (P = 0.0088), high-risk tumors (P < 0.00001), International Neuroblastoma Staging System

(INSS) stage 4 tumors (P < 0.00001), and in children who died (P = 0.034).

Conclusions: Circulating G_D2 appears to be a specific and sensitive tumor biomarker for highrisk/

high-stage neuroblastoma and may prove to be clinically useful as a diagnostic or prognostic

circulating tumor biomarker. G_D2 will be measured prospectively and longitudinally in children

enrolled on a high-risk neuroblastoma treatment trial to assess its ability to measure response to

treatment and predict survival.

This was a retrospective analysis. Serum samples were obtained from several biorepositories. The C₁₈ and C₂₀ lipoforms of G_D2 were measured in the serum samples using a validated HPLC/MS/MS assay