Genomic copy number profiling using circulating free tumor DNA highlights heterogeneity in neuroblastoma
Menée sur 70 patients atteints d'un neuroblastome, cette étude évalue la faisabilité et, par comparaison avec l'analyse de la tumeur primitive au diagnostic, les performances d'une plateforme d'analyse génomique de l'ADN tumoral circulant librement
Purpose: The tumor genomic copy number profile is of prognostic significance in neuroblastoma (NB) patients. We have studied the genomic copy number profile of cell free DNA (cfDNA) and compared this to primary tumor 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 66/70 and 52/70 cases, respectively. An overall identical genomic profile between tumor aCGH and cfDNA was observed in 47 cases (3 NCA, 22 SCA, 22 MNA). In 1 case, cfDNA showed an additional SCA not detected by tumor aCGH. In 4/8 cases with a silent tumor aCGH profile, cfDNA analysis revealed a dynamic profile (3 SCA,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 NB patients, with a concordance of the overall genomic profile in aCGH and cfDNA-dynamic cases of 97%, and a sensitivity of 77%, respectively. Furthermore, NB heterogeneity is highlighted, suggesting that cfDNA might reflect genetic alterations of more aggressive cell clones.
Clinical Cancer Research , résumé, 2015