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

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Bibliographische Detailangaben
Zeitschriftentitel:	International Journal of Cancer
Personen und Körperschaften:	Thole, Theresa M., Toedling, Joern, Sprüssel, Annika, Pfeil, Sebastian, Savelyeva, Larissa, Capper, David, Messerschmidt, Clemens, Beule, Dieter, Groeneveld‐Krentz, Stefanie, Eckert, Cornelia, Gambara, Guido, Henssen, Anton G., Finkler, Sabine, Schulte, Johannes H., Sieber, Anja, Bluethgen, Nils, Regenbrecht, Christian R. A., Künkele, Annette, Lodrini, Marco, Eggert, Angelika, Deubzer, Hedwig E.
In:	International Journal of Cancer, 146, 2020, 4, S. 1031-1041
Format:	E-Article
Sprache:	Englisch
veröffentlicht:	Wiley
Schlagwörter:	Cancer Research Oncology

Details
Zusammenfassung:	<jats:p>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 <jats:italic>MYCN‐</jats:italic>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 <jats:italic>MYCN</jats:italic> 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 four 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.</jats:p>
Umfang:	1031-1041
ISSN:	0020-7136 1097-0215
DOI:	10.1002/ijc.32572