Ribeiro Franclim Ricardo, Meireles Ana Margarida, Rocha Ana Sofia, Teixeira Manuel Rodrigues
Department of Genetics, Portuguese Oncology Institute, Porto, Portugal.
BMC Cancer. 2008 Dec 16;8:371. doi: 10.1186/1471-2407-8-371.
Cell lines are often poorly characterized from a genetic point of view, reducing their usefulness as tumor models. Our purpose was to assess the genetic background of eight commonly used human thyroid carcinoma models and to compare the findings with those reported for primary tumors of the gland.
We used chromosome banding analysis and comparative genomic hybridization to profile eight non-medullary thyroid carcinoma cell lines of papillary (TPC-1, FB2, K1 and B-CPAP), follicular (XTC-1) or anaplastic origin (8505C, C643 and HTH74). To assess the representativeness of the findings, we additionally performed a thorough review of cytogenetic (n = 125) and DNA copy number information (n = 270) available in the literature on clinical samples of thyroid carcinoma.
The detailed characterization of chromosomal markers specific for each cell line revealed two cases of mistaken identities: FB2 was shown to derive from TPC-1 cells, whereas K1 cells have their origin in cell line GLAG-66. All cellular models displayed genomic aberrations of varying complexity, and recurrent gains at 5p, 5q, 8q, and 20q (6/7 cell lines) and losses at 8p, 13q, 18q, and Xp (4/7 cell lines) were seen. Importantly, the genomic profiles were compatible with those of the respective primary tumors, as seen in the meta-analysis of the existing literature data.
We provide the genomic background of seven independent thyroid carcinoma models representative of the clinical tumors of the corresponding histotypes, and highlight regions of recurrent aberrations that may guide future studies aimed at identifying target genes. Our findings further support the importance of routinely performing cytogenetic studies on cell lines, to detect cross-contamination mishaps such as those identified here.
从遗传学角度来看，细胞系的特征通常 poorly characterized，这降低了它们作为肿瘤模型的实用性。我们的目的是评估八种常用的人类甲状腺癌模型的遗传背景，并将结果与该腺体原发性肿瘤的报告结果进行比较。
我们使用染色体显带分析和比较基因组杂交技术对八种非髓样甲状腺癌细胞系进行分析，这些细胞系分别为乳头状（TPC-1、FB2、K1和B-CPAP）、滤泡状（XTC-1）或间变性起源（8505C、C643和HTH74）。为了评估结果的代表性，我们还对甲状腺癌临床样本的文献中可用的细胞遗传学（n = 125）和DNA拷贝数信息（n = 270）进行了全面回顾。
对每个细胞系特异的染色体标志物的详细表征揭示了两例身份错误的情况：FB2被证明源自TPC-1细胞，而K1细胞起源于GLAG-66细胞系。所有细胞模型都显示出不同程度的基因组畸变，发现5p、5q、8q和20q存在复发性增益（6/7个细胞系），8p、13q、18q和Xp存在缺失（4/7个细胞系）。重要的是，正如现有文献数据的荟萃分析所示，基因组图谱与各自原发性肿瘤的图谱相符。
我们提供了七种独立的甲状腺癌模型的基因组背景，这些模型代表了相应组织学类型的临床肿瘤，并突出了复发性畸变区域，这些区域可能指导未来旨在识别靶基因的研究。我们的发现进一步支持了对细胞系常规进行细胞遗传学研究的重要性，以检测此处所识别的交叉污染失误等情况。
