探索乳腺癌中的染色体不稳定性和克隆异质性。
Exploring chromosomal instability and clonal heterogeneity in breast cancer.
发表日期:2024 Sep 01
作者:
Giovanny Castellanos, Laura Valentina Camargo-Herrera, Nelson Rangel, Guillermo Antonio Jiménez-Tobón, María Martínez-Agüero, Milena Rondón-Lagos
来源:
ENDOCRINE-RELATED CANCER
摘要:
染色体不稳定性(CIN)以细胞内染色体数量或结构的波动为特征,是癌症的一个明显标志,使肿瘤在恶劣的条件下茁壮成长。 CIN 是遗传多样性的驱动因素,导致克隆异质性 (CH)。新出现的证据表明,CIN、CH 与乳腺癌 (BC) 患者的预后之间存在潜在相关性,尤其是在人类表皮生长因子受体 2 (HER2) 过度表达的肿瘤中。然而,我们对 CIN 在 BC 其他亚型中的作用的了解有限。此外,尚不清楚 BC 肿瘤中 CIN 水平高于某个阈值是否会对肿瘤生长产生不利影响,或者与升高水平相比,较低至中等水平的 CIN 是否可能与 BC 患者更有利的预后相关。阐明这些关系可能会显着影响 BC 中 CIN 的风险评估和未来治疗方法的制定。本研究旨在评估从诊断为 Luminal A、Luminal B、HER2 或三阴性 BC 的哥伦比亚患者获得的肿瘤组织样本中的 CIN 和 CH,并将其与已确定的临床病理学参数进行比较。本研究的结果表明 BC 患者表现出中等 CIN、高 CH 和稳定的非整倍性。所有这些特征被发现与临床病理特征相关。我们的结果表明,CIN、CH 和非整倍体的识别可以改善癌症风险分层,这有助于阐明临床结果的预测并指导不同 BC 亚型患者的个性化治疗策略。
Chromosomal instability (CIN), characterized by fluctuations in chromosome number or structure within cells, stands out as a hallmark of cancer, enabling tumors to thrive in hostile conditions. CIN serves as a driver of genetic diversity, giving rise to clonal heterogeneity (CH). Emerging evidence points to a potential correlation between CIN, CH, and the prognosis of breast cancer (BC) patients, especially in tumors exhibiting overexpression of the human epidermal growth factor receptor 2 (HER2+). However, our understanding of the role of CIN in other subtypes of BC is limited. Furthermore, it remains unclear whether CIN levels above a certain threshold in BC tumors could adversely affect tumor growth, or if lower to moderate levels of CIN might be associated with a more favorable prognosis for BC patients compared to elevated levels. Elucidating these relationships could significantly influence risk assessment and the formulation of future therapeutic approaches targeting CIN in BC. This study aimed to assess CIN and CH in tumor tissue samples obtained from Colombian patients diagnosed with luminal A, luminal B, HER2+, or triple-negative BC, and compare them with established clinicopathological parameters. The findings of this study indicate that BC patients, exhibit intermediate CIN, high CH, and stable aneuploidy. All these characteristics were found to be related with clinicopathological features. Our results suggest that the identification of CIN, CH and aneuploidy could improve cancer risk stratification, which could help to clarify the prediction of clinical outcomes and guiding personalized therapeutic strategies for patients with different BC subtypes.