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ORIGINAL RESEARCH article
Front. Oncol.
Sec. Cancer Genetics
Volume 14 - 2024 |
doi: 10.3389/fonc.2024.1361603
This article is part of the Research Topic Women in Cancer Genetics Vol III: 2023 View all 3 articles
Patient-Derived Organoid Elucidates the Identical Clonal Origin of Bilateral Breast Cancer with Diverse Molecular Subtypes
Provisionally accepted- Affiliated Zhongshan Hospital of Dalian University, Dalian, Liaoning Province, China
Bilateral breast cancer (BBC), an infrequent breast cancer subtype, has primarily been studied in terms of incidence, prognosis, and through comparative analysis of synchronous (SBBC) and metachronous (MBBC) manifestations. The advent and application of organoid technology hold profound implications for tumor research and clinical management. This study represents the pioneering use of organoid models in BBC research. We established organoid lines from two surgical tumor specimens of a BBC patient, with one line undergoing detailed pathological and genomic analysis. The BBC organoid from the right breast demonstrated a marker expression profile of ER (-), PR (-), HER-2 (0), and Ki67 index 10%, indicating that it may derived from the TNBC tissue. Whole Exome Sequencing (WES) displayed consistent set of Top10 cancer driver genes affected by missense mutations, frameshift mutation, or splice site mutations in three tumor tissues and the organoid samples. The organoids' single nucleotide polymorphisms (SNPs) were more closely aligned with the TNBC tissue than other tumor tissues. Evolutionary analysis suggested that different tumor regions might evolve from a common ancestral layer. In this case, the development of BBC organoids indicated that simultaneous lesions with diverse molecular profiles shared a high degree of consistency in key tumordriving mutations. These findings suggest the feasibility of generating BBC organoids representing various molecular types, accurately replicating significant markers and driver mutations of the originating tumor. Consequently, organoids serve as a valuable in vitro model for exploring treatment strategies and elucidating the underlying mechanisms of BBC.
Keywords: rganoids, Bilateral breast cancer, driver mutations, evolution, Molecular subtypes
Received: 26 Dec 2023; Accepted: 25 Apr 2024.
Copyright: © 2024 Han, Yao, Fang, Chen, Lian, Yao, Chen, Ji, Yu, Wang, Wang and Liang. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence:
Shanshan Liang, Affiliated Zhongshan Hospital of Dalian University, Dalian, Liaoning Province, China
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