小柯机器人

荷兰癌症研究所Jos Jonkers研究团队近日取得一项新成果。经过不懈努力，他们利用患者来源的导管原位癌（DCIS）小鼠-导管内异种移植物生物库鉴定了与侵袭性进展有关的危险因素。相关论文于2023年4月27日发表于国际学术期刊《癌细胞》杂志。

研究人员表征了115个患者来源的小鼠导管内（MIND）DCIS模型，其能够反映在患者中观察到的全部DCIS类型。利用组学和成像数据相结合跟踪DCIS自然进展的可能性，研究人员揭示了与高风险DCIS有关的多种预后因素，包括高级别、HER2扩增、3D生长加剧和高拷贝数畸变增加。此外，异种移植物的依次移植随着时间推移显示出最弱的表型和基因型变化，表明侵入性行为是DCIS的内在表型，并支持多克隆进化模型。

此外，该研究提供了19个可分享的DCIS-MIND模型集合，其涵盖了所有分子亚型。

研究人员表示，导管原位癌是浸润性乳腺癌（IBC）的非专性前体。由于缺乏能够区分高风险和低风险病例的生物标志物，DCIS的治疗方法与早期IBC相似，尽管只有少数未经治疗的病例最终发展为侵袭性病例。

附：英文原文

Title: A living biobank of patient-derived ductal carcinoma in situ mouse-intraductal xenografts identifies risk factors for invasive progression

Author: Stefan J. Hutten, Roebi de Bruijn, Catrin Lutz, Madelon Badoux, Timo Eijkman, Xue Chao, Marta Ciwinska, Michael Sheinman, Hendrik Messal, Andrea Herencia-Ropero, Petra Kristel, Lennart Mulder, Rens van der Waal, Joyce Sanders, Mathilde M. Almekinders, Alba Llop-Guevara, Helen R. Davies, Matthijs J. van Haren, Nathaniel I. Martin, Fariba Behbod, Serena Nik-Zainal, Violeta Serra, Jacco van Rheenen, Esther H. Lips, Lodewyk F.A. Wessels, Jelle Wesseling, Colinda L.G.J. Scheele, Jos Jonkers

Issue&Volume: 2023-04-27

Abstract: Ductal carcinoma in situ (DCIS) is a non-obligate precursor of invasive breast cancer (IBC). Due to a lack of biomarkers able to distinguish high- from low-risk cases, DCIS is treated similar to early IBC even though the minority of untreated cases eventually become invasive. Here, we characterized 115 patient-derived mouse-intraductal (MIND) DCIS models reflecting the full spectrum of DCIS observed in patients. Utilizing the possibility to follow the natural progression of DCIS combined with omics and imaging data, we reveal multiple prognostic factors for high-risk DCIS including high grade, HER2 amplification, expansive 3D growth, and high burden of copy number aberrations. In addition, sequential transplantation of xenografts showed minimal phenotypic and genotypic changes over time, indicating that invasive behavior is an intrinsic phenotype of DCIS and supporting a multiclonal evolution model. Moreover, this study provides a collection of 19 distributable DCIS-MIND models spanning all molecular subtypes.

DOI: 10.1016/j.ccell.2023.04.002

Source: https://www.cell.com/cancer-cell/fulltext/S1535-6108(23)00128-9

Cancer Cell：《癌细胞》，创刊于2002年。隶属于细胞出版社，最新IF：38.585
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