Genomic diversity and BCL9L mutational status in circulating tumor cells predict overall survival in metastatic colorectal cancer.

IF 4.8 2区医学 Q2 CELL BIOLOGY

Cellular Oncology Pub Date : 2025-10-06 DOI:10.1007/s13402-025-01109-x

Joao M Alves, Nuria Estévez-Gómez, Roberto Piñeiro, Laura Muinelo-Romay, Patricia Mondelo-Macía, Mercedes Salgado, Agueda Iglesias-Gómez, Laura Codesido-Prada, Astrid Diez-Martín, Joaquin Cubiella, David Posada

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引用次数: 0

Abstract

Background: Metastatic colorectal cancer (mCRC) remains a major cause of cancer-related mortality, but few noninvasive biomarkers exist to track disease progression or inform treatment strategies. Circulating tumor cells (CTCs) offer a minimally invasive source of tumor material, yet the prognostic significance of their genomic diversity remains unclear.

Methods: We conducted whole-exome sequencing of CTC pools from 29 mCRC patients to characterize their mutational landscape and assess associations with overall survival.

Results: Our analysis revealed substantial variation in mutational burden among patients, with all CTC pools harboring non-silent mutations in key CRC driver genes. Higher genomic diversity in CTC pools was significantly associated with reduced overall survival. Additionally, non-silent mutations in BCL9L emerged as a strong predictor of patient survival.

Conclusion: Genomic diversity and BCL9L mutational status in CTC pools emerged as strong predictors of survival in mCRC, underscoring the potential of CTC genomic profiling as a minimally invasive and clinically relevant prognostic tool in mCRC.

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循环肿瘤细胞的基因组多样性和BCL9L突变状态预测转移性结直肠癌的总生存期。

背景：转移性结直肠癌（mCRC）仍然是癌症相关死亡的主要原因，但很少有无创生物标志物可以跟踪疾病进展或告知治疗策略。循环肿瘤细胞（CTCs）提供了一种微创肿瘤物质来源，但其基因组多样性的预后意义尚不清楚。方法：我们对29例mCRC患者的CTC池进行了全外显子组测序，以表征其突变景观并评估其与总生存期的关系。结果：我们的分析揭示了患者突变负担的实质性变化，所有CTC池都包含关键CRC驱动基因的非沉默突变。CTC池中较高的基因组多样性与总生存率降低显著相关。此外，BCL9L的非沉默突变是患者生存的一个强有力的预测因子。结论：基因组多样性和BCL9L突变状态在CTC池中成为mCRC生存的强有力预测因素，强调了CTC基因组谱分析作为mCRC微创和临床相关预后工具的潜力。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Cellular Oncology ONCOLOGY-CELL BIOLOGY

CiteScore

10.30

自引率

1.50%

发文量

审稿时长

12 months

期刊介绍： The Official Journal of the International Society for Cellular Oncology Focuses on translational research Addresses the conversion of cell biology to clinical applications Cellular Oncology publishes scientific contributions from various biomedical and clinical disciplines involved in basic and translational cancer research on the cell and tissue level, technical and bioinformatics developments in this area, and clinical applications. This includes a variety of fields like genome technology, micro-arrays and other high-throughput techniques, genomic instability, SNP, DNA methylation, signaling pathways, DNA organization, (sub)microscopic imaging, proteomics, bioinformatics, functional effects of genomics, drug design and development, molecular diagnostics and targeted cancer therapies, genotype-phenotype interactions. A major goal is to translate the latest developments in these fields from the research laboratory into routine patient management. To this end Cellular Oncology forms a platform of scientific information exchange between molecular biologists and geneticists, technical developers, pathologists, (medical) oncologists and other clinicians involved in the management of cancer patients. In vitro studies are preferentially supported by validations in tumor tissue with clinicopathological associations.