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人急性T淋巴细胞白血病细胞系Jurkat的高分辨率阵列比较基因组杂交分析:拷贝数改变及其与癌症特征的关联

High-Resolution aCGH Analysis of the Jurkat Cell Line: Copy Number Alterations and Their Association With Cancer Hallmarks.

作者信息

DA Costa Layssa Mota, Ferreira Wallax Augusto Silva, Machado Caio Bezerra, Amorim Carolina Koury Nassar, VAN DEN Berg Ana Virgínia, DE Moraes Filho Manoel Odorico, DE Moraes Maria Elisabete Amaral, DE Souza Lucas Eduardo Botelho, Khayat André Salim, DE Oliveira Edivaldo Herculano Correa, Moreira-Nunes Caroline Aquino

机构信息

Department of Biological Sciences, Oncology Research Center, Federal University of Pará, Belém, Brazil.

Laboratory of Cytogenomics and Environmental Mutagenesis, Environment Section (SAMAM), Evandro Chagas Institute (IEC), Ananindeua, Brazil.

出版信息

Cancer Genomics Proteomics. 2025 Sep-Oct;22(5):824-835. doi: 10.21873/cgp.20539.

Abstract

BACKGROUND/AIM: Cell lines serve as valuable models to study altered cellular signaling pathways, to identify mutations in key oncogenic genes, and to test potential antitumor drugs. The Jurkat cell line, for example, has provided important information about various signaling pathways in lymphoblastic leukemia, establishing most of what is currently known about T-cell receptor (TCR) signaling. However, many aspects of the genome modification of this cell line have not yet been analyzed. To identify genes of potential biological and clinical relevance in acute T-lymphoblastic leukemia (T-ALL), we performed an array comparative genomic hybridization (aCGH) approach on the widely used Jurkat cell line and examined the association of the detected copy number alterations (CNAs) with cancer hallmarks and T-ALL pathogenesis.

MATERIALS AND METHODS

Cells were harvested by using trypsin/EDTA from culture flasks to extract genomic DNA. aCGH experiments were performed on an Agilent microarray platform using the SurePrint G3 Cancer CGH + SNP Microarray 4×180 K. Functional enrichment analysis of all CNAs was performed with the R package g:Profiler2. The association of these alterations with key cancer hallmarks was analyzed using the Cancer Hallmarks web-tool.

RESULTS

Our analysis revealed several novel CNAs, including losses at 5p15.2, 6q27, 10q22.2, 14q11.2, 18q11.2-q12.1, and Xp22.33, as well as gains at 2p11.2, 7p21.2, 7q21.2 and 18p11.32. Genes within these regions were associated with important oncogenic pathways, including 'sustained proliferative signaling', 'tumor suppressor evasion', and 'angiogenesis promotion'.

CONCLUSION

These findings suggest that Jurkat cells may serve as a valuable model for identifying new targets for cancer research. Further studies are required to confirm the phenotypic implications of these variants, which may open new avenues for exploring the functional impact of these alterations and their potential role in the development of therapies.

摘要

背景/目的:细胞系是研究细胞信号通路改变、鉴定关键致癌基因突变以及测试潜在抗肿瘤药物的重要模型。例如,Jurkat细胞系为淋巴细胞白血病中各种信号通路提供了重要信息,确立了目前大多数关于T细胞受体(TCR)信号传导的认知。然而,该细胞系基因组修饰的许多方面尚未得到分析。为了鉴定急性T淋巴细胞白血病(T-ALL)中具有潜在生物学和临床意义的基因,我们对广泛使用的Jurkat细胞系进行了阵列比较基因组杂交(aCGH)分析,并研究了检测到的拷贝数改变(CNA)与癌症特征和T-ALL发病机制的关联。

材料与方法

使用胰蛋白酶/EDTA从培养瓶中收获细胞以提取基因组DNA。在安捷伦微阵列平台上使用SurePrint G3癌症CGH + SNP微阵列4×180 K进行aCGH实验。使用R包g:Profiler2对所有CNA进行功能富集分析。使用癌症特征网络工具分析这些改变与关键癌症特征的关联。

结果

我们的分析揭示了几个新的CNA,包括5p15.2、6q27、10q22.2、14q11.2、18q11.2-q12.1和Xp22.33的缺失,以及2p11.2、7p21.2、7q21.2和18p11.32的增益。这些区域内的基因与重要的致癌途径相关,包括“持续增殖信号传导”、“肿瘤抑制逃避”和“血管生成促进”。

结论

这些发现表明Jurkat细胞可能是识别癌症研究新靶点的有价值模型。需要进一步研究来证实这些变体的表型影响,这可能为探索这些改变的功能影响及其在治疗开发中的潜在作用开辟新途径。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/25e6/12402711/e531008320a1/cgp-22-829-g0001.jpg

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