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Reflection of neuroblastoma intratumor heterogeneity in the new OHC-NB1 disease model

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Item Type:Article
Title:Reflection of neuroblastoma intratumor heterogeneity in the new OHC-NB1 disease model
Creators Name:Thole, T.M. and Toedling, J. and Sprüssel, A. and Pfeil, S. and Savelyeva, L. and Capper, D. and Messerschmidt, C. and Beule, D. and Groeneveld-Krentz, S. and Eckert, C. and Gambara, G. and Henssen, A.G. and Finkler, S. and Schulte, J.H. and Sieber, A. and Bluethgen, N. and Regenbrecht, C.R.A. and Künkele, A. and Lodrini, M. and Eggert, A. and Deubzer, H.E.
Abstract:Accurate modeling of intratumor heterogeneity presents a bottleneck against drug testing. Flexibility in a preclinical platform is also desirable to support assessment of different endpoints. We established the model system, OHC-NB1, from a bone marrow metastasis from a patient diagnosed with MYCN-amplified neuroblastoma and performed whole-exome sequencing on the source metastasis and the different models and passages during model development (monolayer cell line, 3D spheroid culture and subcutaneous xenograft tumors propagated in mice). OHC-NB1 harbors a MYCN amplification in double minutes, 1p deletion, 17q gain and diploid karyotype, which persisted in all models. A total of 80-540 single-nucleotide variants (SNVs) was detected in each sample, and comparisons between the source metastasis and models identified 34 of 80 somatic SNVs to be propagated in the models. Clonal reconstruction using the combined copy number and SNV data revealed marked clonal heterogeneity in the originating metastasis, with 4 clones being reflected in the model systems. The set of OHC-NB1 models represents 43% of somatic SNVs and 23% of the cellularity in the originating metastasis with varying clonal compositions, indicating that heterogeneity is partially preserved in our model system.
Keywords:Embryonal Tumor, Single-Nucleotide Variant Analysis, Copy Number Variation Analysis, Clonal Reconstruction, MYCN Amplification, Preclinical Drug Testing, Animals, Mice
Source:International Journal of Cancer
Page Range:1031-1041
Date:15 February 2020
Official Publication:https://doi.org/10.1002/ijc.32572
PubMed:View item in PubMed

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