Loss of chromosome cytoband 13q14.2 orchestrates breast cancer pathogenesis and drug response.

IF 7.4 1区 医学 Q1 Medicine
Parastoo Shahrouzi, Youness Azimzade, Wioletta Brankiewicz-Kopcinska, Sugandha Bhatia, David Kunke, Derek Richard, Xavier Tekpli, Vessela N Kristensen, Pascal H G Duijf
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引用次数: 0

Abstract

Breast cancer (BCa) is a major global health challenge. The BCa genome often carries extensive somatic copy number alterations (CNAs), including gains/amplifications and losses/deletions. These CNAs significantly affect tumor development, drug response and patient survival. However, how individual CNAs contribute is mostly elusive. We identified loss of chromosome 13q14.2 as a key CNA in BCa, occurring in up to 63% of patients, depending on the subtype, and correlating with poor survival. Through multi-omics and in vitro analyses, we uncover a paradoxical role of 13q14.2 loss, promoting both cell cycle and pro-apoptotic pathways in cancer cells, while also associating with increased NK cell and macrophage populations in the tumor microenvironment. Notably, 13q14.2 loss increases BCa susceptibility to BCL2 inhibitors, both in vitro and in patient-derived xenografts. Thus, 13q14.2 loss could serve as a biomarker for BCa prognosis and treatment, potentially improving outcomes for BCa patients.

染色体细胞带 13q14.2 的缺失协调了乳腺癌的发病机制和药物反应。
乳腺癌(BCa)是一项重大的全球性健康挑战。乳腺癌基因组通常带有广泛的体细胞拷贝数改变(CNA),包括增益/扩增和缺失/缺失。这些 CNAs 会严重影响肿瘤的发展、药物反应和患者生存。然而,单个 CNAs 是如何起作用的目前尚不清楚。我们发现13q14.2染色体缺失是BCa中的一个关键CNA,根据亚型的不同,多达63%的患者会出现该缺失,并与生存率低下相关。通过多组学和体外分析,我们发现了13q14.2缺失的矛盾作用,它促进了癌细胞的细胞周期和促凋亡途径,同时也与肿瘤微环境中NK细胞和巨噬细胞数量的增加有关。值得注意的是,13q14.2 缺失会增加 BCa 对 BCL2 抑制剂的敏感性,无论是在体外还是在患者衍生的异种移植物中。因此,13q14.2缺失可作为BCa预后和治疗的生物标志物,从而改善BCa患者的预后。
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来源期刊
CiteScore
12.00
自引率
0.00%
发文量
76
审稿时长
12 weeks
期刊介绍: Breast Cancer Research, an international, peer-reviewed online journal, publishes original research, reviews, editorials, and reports. It features open-access research articles of exceptional interest across all areas of biology and medicine relevant to breast cancer. This includes normal mammary gland biology, with a special emphasis on the genetic, biochemical, and cellular basis of breast cancer. In addition to basic research, the journal covers preclinical, translational, and clinical studies with a biological basis, including Phase I and Phase II trials.
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