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Reflection of neuroblastoma intratumor heterogeneity in the new OHC‐NB1 disease model
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| Zeitschriftentitel: | International Journal of Cancer |
|---|---|
| Personen und Körperschaften: | , , , , , , , , , , , , , , , , , , , , |
| In: | International Journal of Cancer, 146, 2020, 4, S. 1031-1041 |
| Format: | E-Article |
| Sprache: | Englisch |
| veröffentlicht: |
Wiley
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| Schlagwörter: |
| author_facet |
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. 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. |
|---|---|
| author |
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. |
| spellingShingle |
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. International Journal of Cancer Reflection of neuroblastoma intratumor heterogeneity in the new OHC‐NB1 disease model Cancer Research Oncology |
| author_sort |
thole, theresa m. |
| spelling |
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. 0020-7136 1097-0215 Wiley Cancer Research Oncology http://dx.doi.org/10.1002/ijc.32572 <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> Reflection of neuroblastoma intratumor heterogeneity in the new OHC‐NB1 disease model International Journal of Cancer |
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International Journal of Cancer |
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| title |
Reflection of neuroblastoma intratumor heterogeneity in the new OHC‐NB1 disease model |
| title_unstemmed |
Reflection of neuroblastoma intratumor heterogeneity in the new OHC‐NB1 disease model |
| title_full |
Reflection of neuroblastoma intratumor heterogeneity in the new OHC‐NB1 disease model |
| title_fullStr |
Reflection of neuroblastoma intratumor heterogeneity in the new OHC‐NB1 disease model |
| title_full_unstemmed |
Reflection of neuroblastoma intratumor heterogeneity in the new OHC‐NB1 disease model |
| title_short |
Reflection of neuroblastoma intratumor heterogeneity in the new OHC‐NB1 disease model |
| title_sort |
reflection of neuroblastoma intratumor heterogeneity in the new ohc‐nb1 disease model |
| topic |
Cancer Research Oncology |
| url |
http://dx.doi.org/10.1002/ijc.32572 |
| publishDate |
2020 |
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1031-1041 |
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<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> |
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| author | 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. |
| author_facet | 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., 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. |
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| description | <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> |
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| spelling | 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. 0020-7136 1097-0215 Wiley Cancer Research Oncology http://dx.doi.org/10.1002/ijc.32572 <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> Reflection of neuroblastoma intratumor heterogeneity in the new OHC‐NB1 disease model International Journal of Cancer |
| spellingShingle | 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., International Journal of Cancer, Reflection of neuroblastoma intratumor heterogeneity in the new OHC‐NB1 disease model, Cancer Research, Oncology |
| title | Reflection of neuroblastoma intratumor heterogeneity in the new OHC‐NB1 disease model |
| title_full | Reflection of neuroblastoma intratumor heterogeneity in the new OHC‐NB1 disease model |
| title_fullStr | Reflection of neuroblastoma intratumor heterogeneity in the new OHC‐NB1 disease model |
| title_full_unstemmed | Reflection of neuroblastoma intratumor heterogeneity in the new OHC‐NB1 disease model |
| title_short | Reflection of neuroblastoma intratumor heterogeneity in the new OHC‐NB1 disease model |
| title_sort | reflection of neuroblastoma intratumor heterogeneity in the new ohc‐nb1 disease model |
| title_unstemmed | Reflection of neuroblastoma intratumor heterogeneity in the new OHC‐NB1 disease model |
| topic | Cancer Research, Oncology |
| url | http://dx.doi.org/10.1002/ijc.32572 |