Background : In neuroblastoma (NB), characterization of the overall tumor genomic copy number profile is important for treatment stratification. We have studied the genomic copy number profile of circulating cell free tumor DNA (ctDNA) and compared this to the aCGH of the primary tumour.
Methods : In a series of 70 NB patients for whom aCGH had been done on tumor tissue and for whom plasma was available for ctDNA extraction, ctDNA copy number profiling was performed using the OncoScan® platform.
Results : Higher ctDNA quantities and qualities were observed in advanced stages of disease. Interpretable ctDNA copy number profiles were obtained in 66/70 cases. An overall identical genomic profile between aCGH of the primary tumor tissue and ctDNA was observed in 47cases, with an additional segmental chromosome alteration seen in ctDNA in 1 case. In 14 other cases, ctDNA analysis did not reveal any copy number changes, 10/14 of these cases having localized disease. Finally, in 4/8 cases with a silent aGCH profile, ctDNA analysis revealed a dynamic profile. A total of 397 breakpoints common to both samples, primary tumor and ctDNA of any given patient, were identified (mean: 10 common breakpoints per case; range 1–37 breakpoints). In addition, 25 breakpoints were only seen by aCGH on the primary tumor, and 33 breakpoints were seen in ctDNA only, including two cases with interstitial gains encompassing IGFR1, and one alteration targeting TERT.
Conclusion : These results demonstrate the feasibility of copy number profiling using ctDNA in NB patients at the time of diagnosis. Given the possibility of evolution of copy number profiles in NB progression, the possibility of performing sequential analysis using ctDNA is of importance. This study further highlights the heterogeneity of NB. Further studies will help to determine the cellular origin of ctDNA and whether it represents genetic alterations from more aggressive tumour cells.