Age-dependent reference intervals in children for the disialoganglioside, GD2, a circulating tumor biomarker for the childhood cancer, neuroblastoma

Background: The disialoganglioside GD2 is a circulating tumor biomarker for the childhood cancer, neuroblastoma. This study establishes reference intervals for GD2 concentration in children within the age range where neuroblastoma commonly occurs. Methods: Leftover plasma samples taken for routine clinical laboratory tests from children without cancer were collected and assayed for the 18-carbon fatty acid chain length lipoform of GD2 using a validated high-pressure liquid chromatography tandem mass spectrometry method with a lower limit of quantification of 3 nM. Samples were stratified into 5 age cohorts (0-6 months, 6-12 months, 12-36 months, 3-10 years and > 10 years). Nonparametric statistical methods were used to define the upper bound of the reference interval for each age cohort. Results: GD2 was measurable in 90% of samples from children < 10 years of age and GD2 concentration was agedependent, peaking at 9 months followed by a gradual decline. GD2 was below the lower limit of quantification in 55% of samples in the > 10 years cohort. Upper bounds of reference intervals were 15.5 nM in 0-6 month cohort, 35.1 nM in 6-12 month cohort, 24.9 nM in 12-36 month cohort, 18.4 in 3-10 year cohort and 10.4 nM in > 10 year cohort. Conclusions: Age-dependent reference intervals were defined for circulating GD2 in children. GD2 concentration was highest in the 6-12 month age cohort, which is below the age of most children with high-risk neuroblastoma. The peak GD2 concentration at 9 months may reflect neurodevelopmental events in the brain.