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新建立的胃肠道癌细胞系保留了其亲本肿瘤的基因组和免疫表型特征。

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

机构信息

Institute of Pathology, University Medical Center Mannheim, Medical Faculty Mannheim, Heidelberg University, Theodor-Kutzer-Ufer 1-3, 68167, Mannheim, Germany.

Section of Cancer Genomics, Genetics Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA.

出版信息

Sci Rep. 2020 Oct 21;10(1):17895. doi: 10.1038/s41598-020-74797-0.

Abstract

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.

摘要

人类癌细胞系常被用作研究癌症分子机制和遗传变化的模型系统。然而,该模型因其与原始患者肿瘤的接近度不足而屡遭批评。因此,在分析其生物学特性时,了解在何种程度上人工培养的细胞系反映其相应亲本肿瘤的表型和基因组特征至关重要。为了直接比较患者肿瘤和衍生细胞系之间的分子改变,我们从 4 名胃肠道肿瘤患者中建立了新的癌细胞系。肿瘤实体包括食管癌、结肠癌、直肠癌和胰腺癌。通过免疫组织化学(22 种不同的抗体)、基于阵列的比较基因组杂交和靶向下一代测序(48 基因面板)对患者肿瘤和衍生的低传代细胞系的表型和基因型进行了表征。患者肿瘤和衍生细胞系之间的免疫表型高度一致;细胞系中大多数标志物的表达与各自的亲本肿瘤一致,通常与各自的肿瘤实体特征一致。亲本肿瘤的染色体畸变模式在细胞系中基本保持不变,增益和损失的分布与各自的癌症实体典型一致,尽管存在一些明显的差异。癌症基因突变(如 KRAS、TP53)和微卫星状态也在各自的细胞系衍生物中得到保留。总之,新建立的四个细胞系表现出与其亲本肿瘤密切相关的表型和基因型。因此,新建立的癌细胞系可能是进一步进行药物基因组学研究的有用模型。

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