Newly established gastrointestinal cancer cell lines retain the genomic and immunophenotypic landscape of their parental cancers
Autor: | Steffen Seyfried, Felix Rueckert, Timo Gaiser, Christian Sauer, Tobias Staib, Thomas Ried, Daniela Hirsch, Stephanie H. Witt, David Fiedler |
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Rok vydání: | 2020 |
Předmět: |
Genotype
Colorectal cancer lcsh:Medicine Cell Separation Biology medicine.disease_cause Article Proto-Oncogene Proteins p21(ras) Gastrointestinal cancer Cell Line Tumor Pancreatic cancer Cancer genomics medicine Humans lcsh:Science Cancer models Cancer genetics Gastrointestinal Neoplasms Chromosome Aberrations Comparative Genomic Hybridization Multidisciplinary lcsh:R High-Throughput Nucleotide Sequencing Cancer medicine.disease Immunohistochemistry Phenotype Mutation Cancer research lcsh:Q KRAS Tumor Suppressor Protein p53 Microsatellite Repeats Comparative genomic hybridization |
Zdroj: | Scientific Reports Scientific Reports, Vol 10, Iss 1, Pp 1-11 (2020) |
ISSN: | 2045-2322 |
DOI: | 10.1038/s41598-020-74797-0 |
Popis: | 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. |
Databáze: | OpenAIRE |
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