Background/objective: Mucinous borderline tumors of the ovary (MBOTs) are characterized by their unique histological features and intermediate malignant potential; however, the factors underlying their molecular carcinogenesis and tumor biology remain largely unknown. Developing cell lines from these tumors presents an ongoing challenge. The purpose of this study is to establish MBOT cell lines and characterize their biological features. Methods: Epithelial cells were collected and purified from surgically removed MBOT samples and then stably maintained with an extended life span by overexpressingCyclinD1/CDK4in combination withhuman telomerase reverse transcriptase. The characterization of resulting cell lines was defined by morphology, growth kinetics, functional analysis, whole-exome sequencing, and tumorigenicity in mice. Results: Two independent cell lines, HMucBOT-1 and HMucBOT-2, were successfully established from the tissues of a patient with an MBOT, with the latter showing more aggressive growth capacity. In the patient-derived xenograft model, HMucBOT-1 cells retained the original morphological characteristics of the MBOT, whereas HMucBOT-2 cells displayed a transition to mucinous carcinoma accompanying undifferentiated carcinoma, suggestive of dedifferentiated carcinoma. Genetic analysis of the original tumor sample and HMucBOT-2 cells revealed shared oncogenic mutations. However,KRASamplification and certain copy number alterations were uniquely observed in the HMucBOT-2 cells. Conclusions: The above results indicate that HMucBOT-1 can serve as a preclinical model for investigating the biological behavior of and potential targeted therapies for human MBOTs, with HMucBOT-2 serving as a valuable tool for studying the heterogeneity and genetic diversity of this tumor and explaining the potential causes of treatment failure or relapse.
背景/目的：卵巢黏液性交界性肿瘤（MBOTs）具有独特的组织学特征和中等恶性潜能，但其分子致癌机制和肿瘤生物学基础因素在很大程度上仍不明确。从这类肿瘤中建立细胞系一直是个持续挑战。本研究旨在建立MBOT细胞系并表征其生物学特性。方法：从手术切除的MBOT样本中收集并纯化上皮细胞，通过过表达CyclinD1/CDK4联合人端粒酶逆转录酶实现细胞稳定传代并延长其生命周期。通过形态学、生长动力学、功能分析、全外显子组测序及小鼠致瘤性实验对所得细胞系进行鉴定。结果：从一名MBOT患者的组织中成功建立了两个独立细胞系HMucBOT-1和HMucBOT-2，其中后者表现出更强的侵袭性生长能力。在患者来源异种移植模型中，HMucBOT-1细胞保留了MBOT原有的形态学特征，而HMucBOT-2细胞则呈现向黏液性癌伴未分化癌的转变，提示去分化癌变。对原始肿瘤样本和HMucBOT-2细胞的遗传学分析显示二者存在共同的致癌突变，但KRAS基因扩增及特定拷贝数变异仅在HMucBOT-2细胞中被发现。结论：上述结果表明HMucBOT-1可作为研究人类MBOT生物学行为及潜在靶向治疗的临床前模型，而HMucBOT-2则为探索该肿瘤异质性、遗传多样性及解释治疗失败或复发的潜在原因提供了重要工具。
肿瘤(癌症)患者之家