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腔面B型乳腺癌的染色体不稳定模式与克隆异质性:一项初步研究

Patterns of Chromosomal Instability and Clonal Heterogeneity in Luminal B Breast Cancer: A Pilot Study.

作者信息

Camargo-Herrera Valentina, Castellanos Giovanny, Rangel Nelson, Jiménez-Tobón Guillermo Antonio, Martínez-Agüero María, Rondón-Lagos Milena

机构信息

School of Biological Sciences, Universidad Pedagógica y Tecnológica de Colombia, Tunja 150003, Colombia.

Departamento de Nutrición y Bioquímica, Facultad de Ciencias, Pontificia Universidad Javeriana, Bogotá 110231, Colombia.

出版信息

Int J Mol Sci. 2024 Apr 19;25(8):4478. doi: 10.3390/ijms25084478.

Abstract

Chromosomal instability (CIN), defined by variations in the number or structure of chromosomes from cell to cell, is recognized as a distinctive characteristic of cancer associated with the ability of tumors to adapt to challenging environments. CIN has been recognized as a source of genetic variation that leads to clonal heterogeneity (CH). Recent findings suggest a potential association between CIN and CH with the prognosis of BC patients, particularly in tumors expressing the epidermal growth factor receptor 2 (HER2+). In fact, information on the role of CIN in other BC subtypes, including luminal B BC, is limited. Additionally, it remains unknown whether CIN in luminal B BC tumors, above a specific threshold, could have a detrimental effect on the growth of human tumors or whether low or intermediate CIN levels could be linked to a more favorable BC patient prognosis when contrasted with elevated levels. Clarifying these relationships could have a substantial impact on risk stratification and the development of future therapeutic strategies aimed at targeting CIN in BC. This study aimed to assess CIN and CH in tumor tissue samples from ten patients with luminal B BC and compare them with established clinicopathological parameters. The results of this study reveal that luminal B BC patients exhibit intermediate CIN and stable aneuploidy, both of which correlate with lymphovascular invasion. Our results also provide valuable preliminary data that could contribute to the understanding of the implications of CIN and CH in risk stratification and the development of future therapeutic strategies in BC.

摘要

染色体不稳定(CIN),定义为细胞间染色体数量或结构的变化,被认为是癌症的一个显著特征,与肿瘤适应挑战性环境的能力相关。CIN已被认为是导致克隆异质性(CH)的遗传变异来源。最近的研究结果表明,CIN和CH与乳腺癌患者的预后之间可能存在关联,特别是在表达表皮生长因子受体2(HER2+)的肿瘤中。事实上,关于CIN在其他乳腺癌亚型(包括腔面B型乳腺癌)中的作用的信息有限。此外,尚不清楚腔面B型乳腺癌肿瘤中的CIN超过特定阈值时是否会对人类肿瘤的生长产生不利影响,或者与升高的水平相比,低或中等CIN水平是否与更有利的乳腺癌患者预后相关。阐明这些关系可能会对风险分层以及未来旨在靶向乳腺癌中CIN的治疗策略的开发产生重大影响。本研究旨在评估10例腔面B型乳腺癌患者肿瘤组织样本中的CIN和CH,并将其与既定的临床病理参数进行比较。本研究结果显示,腔面B型乳腺癌患者表现出中等CIN和稳定的非整倍体,两者均与淋巴管浸润相关。我们的结果还提供了有价值的初步数据,有助于理解CIN和CH在乳腺癌风险分层及未来治疗策略开发中的意义。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2abb/11049937/0d47cd940222/ijms-25-04478-g001.jpg

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