Branigan Grace Purvis, Casado-Medrano Victoria, O'Neill Alison B, Ricarte-Filho Julio C, Massoll Nicole, Salwen Madeleine, Spangler Zachary, Scheerer Michele, Williamson Edward K, Bauer Andrew J, Franco Aime T
Division of Endocrinology and Diabetes, Children's Hospital of Philadelphia, Philadelphia, PA 19104, USA.
Department of Pathology, Winthrop P. Rockefeller Cancer Institute, University of Arkansas for Medical Sciences, Little Rock, AR 72205, USA.
Cancers (Basel). 2023 Jan 31;15(3):879. doi: 10.3390/cancers15030879.
The Cancer Genome Atlas study in thyroid cancer exposed the genomic landscape of ~500 PTCs and revealed BRAF-mutant tumors as having different prognosis, contrasting indolent cases and those with more invasive disease. Here, we describe the generation and characterization of six novel BRAF-driven papillary thyroid cancer (PTC) cell lines established from a // mouse model that spontaneously develop thyroid tumors. The novel cell lines were obtained from animals representing a range of developmental stages and both sexes, with the goal of establishing a heterogeneous panel of PTC cell lines sharing a common driver mutation. These cell lines recapitulate the genetics and diverse histopathological features of BRAF-driven PTC, exhibiting differing degrees of growth, differentiation, and invasive potential that may help define mechanisms of pathogenesis underlying the heterogeneity present in the patient population. We demonstrate that these cell lines can be used for a variety of in vitro applications and can maintain the potential for in vivo transplantation into immunocompetent hosts. We believe that these novel cell lines will provide powerful tools for investigating the molecular basis of thyroid cancer progression and will lead to the development of more personalized diagnostic and treatment strategies for BRAF-driven PTC.
癌症基因组图谱（The Cancer Genome Atlas）对甲状腺癌的研究揭示了约500例乳头状甲状腺癌（PTC）的基因组格局，并发现BRAF突变型肿瘤具有不同的预后，惰性病例与侵袭性更强的病例形成对比。在此，我们描述了从自发发生甲状腺肿瘤的小鼠模型中建立的六种新型BRAF驱动的乳头状甲状腺癌细胞系的产生及特性。这些新型细胞系取自代表不同发育阶段和性别的动物，目的是建立一组具有共同驱动突变的异质性PTC细胞系。这些细胞系概括了BRAF驱动的PTC的遗传学和多样的组织病理学特征，表现出不同程度的生长、分化和侵袭潜能，这可能有助于确定患者群体中异质性的发病机制。我们证明，这些细胞系可用于多种体外应用，并能保持在免疫健全宿主中进行体内移植的潜力。我们相信，这些新型细胞系将为研究甲状腺癌进展的分子基础提供有力工具，并将推动针对BRAF驱动的PTC开发更个性化的诊断和治疗策略。
