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Newly established gastrointestinal cancer cell lines retain the genomic and immunophenotypic landscape of their parental cancers

Human cancer cell lines are frequently used as model systems to study molecular mechanisms and genetic changes in cancer. However, the model is repeatedly criticized for its lack of proximity to original patient tumors. Therefore, understanding to what extent cell lines cultured under artificial con...

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Autores principales: Hirsch, Daniela, Seyfried, Steffen, Staib, Tobias, Fiedler, David, Sauer, Christian, Ried, Thomas, Witt, Stephanie, Rueckert, Felix, Gaiser, Timo
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7578805/
https://www.ncbi.nlm.nih.gov/pubmed/33087752
http://dx.doi.org/10.1038/s41598-020-74797-0
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author Hirsch, Daniela
Seyfried, Steffen
Staib, Tobias
Fiedler, David
Sauer, Christian
Ried, Thomas
Witt, Stephanie
Rueckert, Felix
Gaiser, Timo
author_facet Hirsch, Daniela
Seyfried, Steffen
Staib, Tobias
Fiedler, David
Sauer, Christian
Ried, Thomas
Witt, Stephanie
Rueckert, Felix
Gaiser, Timo
author_sort Hirsch, Daniela
collection PubMed
description Human cancer cell lines are frequently used as model systems to study molecular mechanisms and genetic changes in cancer. However, the model is repeatedly criticized for its lack of proximity to original patient tumors. Therefore, understanding to what extent cell lines cultured under artificial conditions reflect the phenotypic and genomic profiles of their corresponding parental tumors is crucial when analyzing their biological properties. To directly compare molecular alterations between patient tumors and derived cell lines, we have established new cancer cell lines from four patients with gastrointestinal tumors. Tumor entities comprised esophageal cancer, colon cancer, rectal cancer and pancreatic cancer. Phenotype and genotype of both patient tumors and derived low-passage cell lines were characterized by immunohistochemistry (22 different antibodies), array-based comparative genomic hybridization and targeted next generation sequencing (48-gene panel). The immunophenotype was highly consistent between patient tumors and derived cell lines; the expression of most markers in cell lines was concordant with the respective parental tumor and characteristic for the respective tumor entities in general. The chromosomal aberration patterns of the parental tumors were largely maintained in the cell lines and the distribution of gains and losses was typical for the respective cancer entity, despite a few distinct differences. Cancer gene mutations (e.g., KRAS, TP53) and microsatellite status were also preserved in the respective cell line derivates. In conclusion, the four examined newly established cell lines exhibited a phenotype and genotype closely recapitulating their parental tumor. Hence, newly established cancer cell lines may be useful models for further pharmacogenomic studies.
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spelling pubmed-75788052020-10-23 Newly established gastrointestinal cancer cell lines retain the genomic and immunophenotypic landscape of their parental cancers Hirsch, Daniela Seyfried, Steffen Staib, Tobias Fiedler, David Sauer, Christian Ried, Thomas Witt, Stephanie Rueckert, Felix Gaiser, Timo Sci Rep Article Human cancer cell lines are frequently used as model systems to study molecular mechanisms and genetic changes in cancer. However, the model is repeatedly criticized for its lack of proximity to original patient tumors. Therefore, understanding to what extent cell lines cultured under artificial conditions reflect the phenotypic and genomic profiles of their corresponding parental tumors is crucial when analyzing their biological properties. To directly compare molecular alterations between patient tumors and derived cell lines, we have established new cancer cell lines from four patients with gastrointestinal tumors. Tumor entities comprised esophageal cancer, colon cancer, rectal cancer and pancreatic cancer. Phenotype and genotype of both patient tumors and derived low-passage cell lines were characterized by immunohistochemistry (22 different antibodies), array-based comparative genomic hybridization and targeted next generation sequencing (48-gene panel). The immunophenotype was highly consistent between patient tumors and derived cell lines; the expression of most markers in cell lines was concordant with the respective parental tumor and characteristic for the respective tumor entities in general. The chromosomal aberration patterns of the parental tumors were largely maintained in the cell lines and the distribution of gains and losses was typical for the respective cancer entity, despite a few distinct differences. Cancer gene mutations (e.g., KRAS, TP53) and microsatellite status were also preserved in the respective cell line derivates. In conclusion, the four examined newly established cell lines exhibited a phenotype and genotype closely recapitulating their parental tumor. Hence, newly established cancer cell lines may be useful models for further pharmacogenomic studies. Nature Publishing Group UK 2020-10-21 /pmc/articles/PMC7578805/ /pubmed/33087752 http://dx.doi.org/10.1038/s41598-020-74797-0 Text en © The Author(s) 2020 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/.
spellingShingle Article
Hirsch, Daniela
Seyfried, Steffen
Staib, Tobias
Fiedler, David
Sauer, Christian
Ried, Thomas
Witt, Stephanie
Rueckert, Felix
Gaiser, Timo
Newly established gastrointestinal cancer cell lines retain the genomic and immunophenotypic landscape of their parental cancers
title Newly established gastrointestinal cancer cell lines retain the genomic and immunophenotypic landscape of their parental cancers
title_full Newly established gastrointestinal cancer cell lines retain the genomic and immunophenotypic landscape of their parental cancers
title_fullStr Newly established gastrointestinal cancer cell lines retain the genomic and immunophenotypic landscape of their parental cancers
title_full_unstemmed Newly established gastrointestinal cancer cell lines retain the genomic and immunophenotypic landscape of their parental cancers
title_short Newly established gastrointestinal cancer cell lines retain the genomic and immunophenotypic landscape of their parental cancers
title_sort newly established gastrointestinal cancer cell lines retain the genomic and immunophenotypic landscape of their parental cancers
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7578805/
https://www.ncbi.nlm.nih.gov/pubmed/33087752
http://dx.doi.org/10.1038/s41598-020-74797-0
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