Chromosomal instability substantiates poor prognosis in patients with diffuse large B-cell lymphoma.
Chromosomal instability substantiates poor prognosis in patients with diffuse large B-cell lymphoma.
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DOI：
10.1158/1078-0432.ccr-11-2049
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发表时间：
2011-12-15
期刊：
影响因子：
--
通讯作者：
Compton DA
中科院分区：
文献类型：
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作者：
Bakhoum SF;Danilova OV;Kaur P;Levy NB;Compton DA
染色体不稳定性（CIN）在肿瘤发生中的具体作用一直是一个猜测问题。在某种程度上，这是由于直接观察染色体错误分离事件的挑战以及无法区分CIN的作用，CIN由染色体错误分离率增加组成，非整倍性是一种非二倍体染色体数目的状态。在这里，我们通过直接测量肿瘤细胞（在经历后期时固定）来检查CIN对诊断为弥漫性大B细胞淋巴瘤（DLBCL）的患者预后的贡献，以获得染色体错误分离的证据。来自一组54名患者的H& E染色样本用于检查染色体错误分离频率与患者预后、总生存率和对治疗的反应之间的关系。我们发现，染色体错误分离的频率增加两倍，导致治疗后总生存率降低24%，无复发生存率降低48%。染色体错误分离增加患者的死亡风险比为2.31，这些患者更可能出现较高的肿瘤分期，表现出肿瘤骨髓受累，并获得较高的国际预后指数（IPI）评分。DLBCL中染色体错误分离率的增加证实了较差的结局和不良预后。这可能是由于肿瘤细胞的异质性增加，导致更大的适应偏好，以响应外部压力，如转移和药物治疗。我们认为，靶向CIN将改善预后和改善对化疗药物的反应。
The specific role of Chromosomal Instability (CIN) in tumorigenesis has been a matter of conjecture. In part, this is due to the challenge of directly observing chromosome mis-segregation events as well as the inability to distinguish the role of CIN, which consists of increased rates of chromosome mis-segregation, from that of aneuploidy, which is a state of non-diploid chromosome number. Here, we examine the contribution of CIN to the prognosis of patients diagnosed with Diffuse Large B-Cell Lymphoma (DLBCL) by directly surveying tumor cells, fixed while undergoing anaphase, for evidence of chromosome mis-segregation. H&E-stained samples from a cohort of 54 patients were used to examine the relationship between frequencies of chromosome mis-segregation and patient prognosis, overall survival, and response to treatment. We show that a two-fold increase in the frequency of chromosome mis-segregation led to a 24% decrease in overall survival and 48% decrease in relapse-free survival after treatment. The hazard ratio of death in patients with increased chromosome mis-segregation was 2.31 and these patients were more likely to present with higher tumor stage, exhibit tumor bone marrow involvement, and receive a higher International Prognostic Index (IPI) score. Increased rates of chromosome mis-segregation in DLBCL substantiate inferior outcome and poor prognosis. This is likely due to increased heterogeneity of tumor cells leading to a larger predilection for adaptation in response to external pressures such as metastasis and drug treatments. We propose that targeting CIN would yield improved prognosis and improved response to chemotherapeutic drugs.