Intraductal tubulopapillary neoplasm (ITPN) is a distinct precancerous lesion in the pancreas with unique clinical and molecular features. Although in vitro studies in two-dimensional culture have led to numerous important insights in pancreatic cancer, such models are currently lacking for precancerous lesions. In this study, we report the generation and characterization of a cell line from a human pancreatic ITPN. Neoplastic cells were initially cultured in a three-dimensional organoid system, followed by transfer to two-dimensional culture. RNA sequencing revealed a gene expression profile consistent with pancreatic ductal origin, and whole genome sequencing identified many somatic mutations (including in genes involved in DNA repair and Wnt signaling) and structural rearrangements. In vitro characterization of the tumorigenic potential demonstrated a phenotype between that of normal pancreatic ductal cells and cancer cell lines. This cell line represents a valuable resource for interrogation of unique ITPN biology, as well as precancerous pancreatic lesions more generally.

导管内小管乳头状肿瘤 (ITPN) 是胰腺中一种独特的癌前病变，具有独特的临床和分子特征。尽管二维培养的体外研究已经对胰腺癌产生了许多重要的见解，但目前缺乏用于癌前病变的此类模型。在这项研究中，我们报告了人类胰腺 ITPN 细胞系的产生和表征。肿瘤细胞最初在三维类器官系统中培养，然后转移到二维培养。RNA 测序揭示了与胰腺导管起源一致的基因表达谱，全基因组测序确定了许多体细胞突变（包括参与 DNA 修复和 Wnt 信号传导的基因）和结构重排。致瘤潜力的体外表征表明正常胰腺导管细胞和癌细胞系之间的表型。该细胞系代表了一种宝贵的资源，可用于研究独特的 ITPN 生物学以及更普遍的胰腺癌前病变。