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

Jurkat细胞系的高分辨率aCGH分析:拷贝数变异及其与癌症特征的关联

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作者:Layssa Mota DA Costa # ,Wallax Augusto Silva Ferreira # ,Caio Bezerra Machado ,Carolina Koury Nassar Amorim ,Ana Virgínia VAN DEN Berg ,Manoel Odorico DE Moraes Filho ,Maria Elisabete Amaral DE Moraes ,Lucas Eduardo Botelho DE Souza ,André Salim Khayat ,Edivaldo Herculano Correa DE Oliveira ,Caroline Aquino Moreira-Nunes
BACKGROUND/AIM: Cell lines serve as valuable in vitro 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.

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