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| Status |
Public on Aug 31, 2017 |
| Title |
Impact of disseminated neuroblastoma cells on the identification of the relapse seeding clone |
| Organism |
Homo sapiens |
| Experiment type |
Genome variation profiling by SNP array
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| Summary |
Background: Since the high relapse rate is considered to be responsible for the poor survival of stage M neuroblastoma patients, we tested whether the genomic information of bone marrow-derived disseminated tumor cells (DTCs) would help to better understand tumor evolution and to characterize the relapse-seeding clone.
Methods: Seven samples from different regions of a primary tumor of a stage M neuroblastoma patient, corresponding DTCs at diagnosis, and DTCs and a metastatic tumor at relapse were analyzed by a high-density SNP array. Relapse-associated chromosomal aberrations found in this case were then validated in DTCs and tumor samples of 154 stage M neuroblastoma patients.
Findings: In this case study, unique aberrations were evident in certain tissue/time points aside from a high concordance of genomic aberrations between all analyzed samples. Surprisingly, DTCs at diagnosis, and DTCs and the metastatic tumor at relapse all displayed a terminal deletion in 1q which was not detected in any of the primary tumor samples.
In the validation cohort, 1q terminal deletions were found with a higher frequency in DTCs at diagnosis (17.8%) and at relapse (27.5%) compared to primary tumors (11%). 1q deletions were significantly associated with 19q and ATRX deletions. The presence of each individual aberration in the diagnostic DTCs was associated with an increased likelihood of an adverse event and in case of 19q deletion with a decreased overall survival. Moreover, PTPRD deletion and loss of chromosome Y had significantly higher frequencies in the relapse samples compared to the diagnostic samples.
Interpretation: These data strongly suggest a branched clonal evolution and a parallel progression of primary and metastatic tumor cells. In addition, the higher frequency of relapse-associated genomic aberrations in the diagnostic DTCs compared to the primary tumors and their effect on the event-free survival rate indicate that analysis of DTCs at diagnosis may provide a higher probability for detecting the relapse-seeding clone compared to the primary tumor.
Background: Since the high relapse rate is considered to be responsible for the poor survival of stage M neuroblastoma patients, we tested whether the genomic information of bone marrow-derived disseminated tumor cells (DTCs) would help to better understand tumor evolution and to characterize the relapse-seeding clone.
Methods: Seven samples from different regions of a primary tumor of a stage M neuroblastoma patient, corresponding DTCs at diagnosis, and DTCs and a metastatic tumor at relapse were analyzed by a high-density SNP array. Relapse-associated chromosomal aberrations found in this case were then validated in DTCs and tumor samples of 154 stage M neuroblastoma patients.
Findings: In this case study, unique aberrations were evident in certain tissue/time points aside from a high concordance of genomic aberrations between all analyzed samples. Surprisingly, DTCs at diagnosis, and DTCs and the metastatic tumor at relapse all displayed a terminal deletion in 1q which was not detected in any of the primary tumor samples.
In the validation cohort, 1q terminal deletions were found with a higher frequency in DTCs at diagnosis (17.8%) and at relapse (27.5%) compared to primary tumors (11%). 1q deletions were significantly associated with 19q and ATRX deletions. The presence of each individual aberration in the diagnostic DTCs was associated with an increased likelihood of an adverse event and in case of 19q deletion with a decreased overall survival. Moreover, PTPRD deletion and loss of chromosome Y had significantly higher frequencies in the relapse samples compared to the diagnostic samples.
Interpretation: These data strongly suggest a branched clonal evolution and a parallel progression of primary and metastatic tumor cells. In addition, the higher frequency of relapse-associated genomic aberrations in the diagnostic DTCs compared to the primary tumors and their effect on the event-free survival rate indicate that analysis of DTCs at diagnosis may provide a higher probability for detecting the relapse-seeding clone compared to the primary tumor.
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| Overall design |
Affymetrix CytoScan HD arrays were performed according to the manufacturer's directions on DNA extracted from bone marrow or tumor samples.
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| Contributor(s) |
Abbasi MR, Rifatbegovic F, Brunner C, Mann G, Ziegler A, Pötschger U, Crazzolara R, Ussowicz M, Benesch M, Ebetsberger-Dachs G, Lode H, Chan GC, Jones N, Ladenstein R, Ambros IM, Ambros PF |
| Citation(s) |
28228384 |
| Submission date |
Jul 12, 2016 |
| Last update date |
Jul 13, 2018 |
| Contact name |
Peter. F. Ambros |
| Organization name |
Children's Cancer Research Institute
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| Department |
Tumor Biology
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| Lab |
4
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| Street address |
Zimmermannplatz 10
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| City |
Vienna |
| ZIP/Postal code |
1090 |
| Country |
Austria |
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| Platforms (1) |
| GPL16131 |
[CytoScanHD_Array] Affymetrix CytoScan HD Array |
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| Samples (214)
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| Relations |
| BioProject |
PRJNA328765 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE84291_RAW.tar |
23.2 Gb |
(http)(custom) |
TAR (of CEL, CYCHP) |
| Processed data provided as supplementary file |
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