The
tumor genomic copy number profile is of prognostic significance in
neuroblastoma patients. We have studied the genomic copy number profile of
cell-free DNA (
cfDNA) and compared this with primary
tumor arrayCGH (aCGH) at diagnosis.
EXPERIMENTAL DESIGN: In 70 patients,
cfDNA genomic copy number profiling was performed using the OncoScan platform. The profiles were classified according to the overall pattern, including numerical chromosome alterations (NCA), segmental chromosome alterations (SCA), and MYCN amplification (MNA).
RESULTS: Interpretable and dynamic
cfDNA profiles were obtained in 66 of 70 and 52 of 70 cases, respectively. An overall identical genomic profile between
tumor aCGH and
cfDNA was observed in 47 cases (3 NCAs, 22 SCAs, 22 MNAs). In one case,
cfDNA showed an additional SCA not detected by
tumor aCGH. In 4 of 8 cases with a silent
tumor aCGH profile,
cfDNA analysis revealed a dynamic profile (3 SCAs, 1 NCA). In 14 cases,
cfDNA analysis did not reveal any copy number changes. A total of 378 breakpoints common to the primary
tumor and
cfDNA of any given patient were identified, 27 breakpoints were seen by
tumor aCGH, and 54 breakpoints were seen in
cfDNA only, including two cases with interstitial IGFR1 gains and two alterations targeting TERT CONCLUSIONS: These results demonstrate the feasibility of
cfDNA copy number profiling in
neuroblastoma patients, with a concordance of the overall genomic profile in aCGH and
cfDNA dynamic cases of 97% and a sensitivity of 77%, respectively. Furthermore,
neuroblastoma heterogeneity is highlighted, suggesting that
cfDNA might reflect genetic alterations of more aggressive cell clones. Clin
Cancer Res; 22(22); 5564-73. ©2016 AACRSee related commentary by Janku and Kurzrock, p. 5400.