Department of Otolaryngology - Head and Neck Surgery, University of Michigan Medical School, Ann Arbor, Michigan.
Department of Pathology, University of Michigan Medical School, Ann Arbor, Michigan.
Head Neck. 2019 Sep;41(9):3114-3124. doi: 10.1002/hed.25803. Epub 2019 May 15.
Laryngeal squamous cell carcinomas (LSCCs) have a high risk of recurrence and poor prognosis. Patient-derived cancer cell lines remain important preclinical models for advancement of new therapeutic strategies, and comprehensive characterization of these models is vital in the precision medicine era.
We performed exome and transcriptome sequencing as well as copy number analysis of a panel of LSCC-derived cell lines that were established at the University of Michigan and are used in laboratories worldwide.
We observed a complex array of alterations consistent with those reported in The Cancer Genome Atlas head and neck squamous cell carcinoma project, including aberrations in PIK3CA, EGFR, CDKN2A, TP53, and NOTCH family and FAT1 genes. A detailed analysis of FAT family genes and associated pathways showed disruptions to these genes in most cell lines.
The molecular profiles we have generated indicate that as a whole, this panel recapitulates the molecular diversity observed in patients and will serve as useful guides in selecting cell lines for preclinical modeling.
喉鳞状细胞癌（LSCC）具有较高的复发风险和预后不良。患者来源的癌细胞系仍然是推进新治疗策略的重要临床前模型，在精准医学时代，对这些模型进行全面表征至关重要。
我们对一组在密歇根大学建立并在全球实验室中使用的 LSCC 衍生细胞系进行了外显子组和转录组测序以及拷贝数分析。
我们观察到一系列与头颈鳞状细胞癌项目的癌症基因组图谱报告一致的复杂改变，包括 PIK3CA、EGFR、CDKN2A、TP53 和 NOTCH 家族和 FAT1 基因的异常。对 FAT 家族基因及其相关途径的详细分析表明，大多数细胞系中这些基因都受到了破坏。
我们生成的分子谱表明，作为一个整体，该细胞系重现了患者中观察到的分子多样性，并将作为临床前建模中选择细胞系的有用指南。
