Li Hui, Ngan Hoi-Lam, Liu Yuchen, Chan Helen Hoi Yin, Poon Peony Hiu Yan, Yeung Chun Kit, Peng Yibing, Lam Wai Yip, Li Benjamin Xiaoyi, He Yukai, Lui Vivian Wai Yan
School of Biomedical Sciences, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong SAR, China.
Department of Medicine, Medical College of Georgia, Augusta University, Augusta, GA 30912, USA.
Cancers (Basel). 2020 Oct 12;12(10):2935. doi: 10.3390/cancers12102935.
Immunocompetent metastatic head and neck cancer (HNC) models, although scarce, can help understanding cancer progression and therapy responses in vivo. Their comprehensive genome characterizations are essential for translational research. We first exome-sequenced the two most widely used spontaneous metastatic immunocompetent models, namely AT-84 and SCC VII, followed by comprehensive genomic analyses with three prior-sequenced models (MOC2, MOC2-10, and 4MOSC2), together with patient tumors for utility assessment. AT-84 and SCC VII bear high HNC tumor resemblance regarding mutational signatures-, Fanconi anemia, and MAPK and PI3K pathway defects. Collectively, the five models harbor genetic aberrations across 10 cancer hallmarks and 14 signaling pathways and machineries (metabolic, epigenetic, immune evasion), to extents similar in patients. Immune defects in (, , , and ), , , , , , and are identified. Invasion/metastatic genome analyses first highlight potential druggable and mutations, for advanced/metastatic oral cavity cancer, as well as known metastasis players (, , , and ) frequently captured by all models. Notable immunotherapy and precision druggable targets (, , , /, , and ) and three druggable hubs (RTK family, MAPK, and DNA repair pathways) are frequently represented by these models. Immunocompetent metastatic HNC models are worth developing to address therapy- and invasion/metastasis-related questions in host immunity contexts.
具有免疫活性的转移性头颈癌（HNC）模型虽然稀缺，但有助于在体内理解癌症进展和治疗反应。它们全面的基因组特征对于转化研究至关重要。我们首先对两种最广泛使用的自发转移性具有免疫活性的模型，即AT - 84和SCC VII进行外显子测序，随后对三个先前测序的模型（MOC2、MOC2 - 10和4MOSC2）以及患者肿瘤进行综合基因组分析以进行效用评估。AT - 84和SCC VII在突变特征、范可尼贫血以及MAPK和PI3K通路缺陷方面与HNC肿瘤高度相似。总体而言，这五个模型在10个癌症标志以及14个信号通路和机制（代谢、表观遗传、免疫逃逸）中存在基因畸变，其程度与患者相似。在（ 、 、 、 ）、 、 、 、 、 、 和 中发现了免疫缺陷。侵袭/转移基因组分析首先突出了晚期/转移性口腔癌潜在的可靶向治疗的 和 突变，以及所有模型中经常检测到的已知转移相关因子（ 、 、 、 ）。这些模型中经常出现显著的免疫治疗和精准可靶向治疗靶点（ 、 、 、 / 、 、 ）以及三个可靶向治疗枢纽（RTK家族、MAPK和DNA修复通路）。具有免疫活性的转移性HNC模型对于解决宿主免疫背景下与治疗以及侵袭/转移相关的问题而言值得开发。
