Chromothripsis and Copy Number Variation as Drivers of Precision Diagnostics in Lymphoma

The field of lymphoma genomics has witnessed groundbreaking advances in recent years, particularly in understanding the complex genetic events underlying disease onset and progression. Among the most prominent discoveries are chromothripsis, catastrophic chromosomal rearrangements and widespread copy number variations, both of which can substantially influence tumor biology and patient prognosis. Traditional diagnostic methods, including karyotyping and targeted molecular assays, often fall short in detecting these intricate genomic alterations, especially when multiple events co-occur or are cryptic in nature. Recent studies have spotlighted the potential of optical genome mapping (OGM), a technology capable of revealing structural variations (SVs) and CNVs in a single assay, to bridge this diagnostic gap. While OGM has been extensively applied to characterize acute leukemias, current data for lymphoid neoplasms, such as lymphomas, remain both sparse and preliminary.Pioneering research has demonstrated that OGM markedly enhances the sensitivity and specificity of genomic characterization in hematological malignancies compared to standard cytogenetic and molecular techniques. In lymphoma, the identification of chromothripsis events and recurring copy number alterations has already begun to influence our understanding of disease mechanisms, risk stratification, and therapeutic targeting. However, significant gaps remain: most available data pertain to small cohorts or individual case studies, and comprehensive, systematic analyses of chromothripsis and CNVs in diverse lymphoma subtypes are lacking. Furthermore, questions persist on integrating these findings into routine clinical algorithms, optimizing diagnostic workflows, and elucidating the utility of OGM versus established ancillary assays.This Research Topic aims to advance knowledge on the role of chromothripsis and copy number variation in driving precision diagnostics for lymphoma. It seeks to clarify the clinical significance of structural genomic alterations detected by state-of-the-art technologies like OGM, and to explore how these findings can improve classification, prognosis, and therapeutic planning for patients. We particularly welcome contributions that address the challenges of validating OGM-based findings in large cohorts, the translational bridge between research and clinical practice, and novel insights into biologically relevant SVs and CNVs.To gather further insights in the application of advanced genomic technologies and their impact on lymphoma diagnosis and management, we welcome articles addressing, but not limited to, the following themes:- Mechanisms and consequences of chromothripsis and CNVs in lymphoma pathogenesis.- Clinical validation and comparative analysis of OGM, NGS, and classical cytogenetic assays.- Integration of OGM findings into diagnostic and prognostic workflows.- Studies on CNV/structural variations in lymphoma subtypes.- Emerging therapeutic implications and personalized care guided by SV and CNV profiles.- Limitations, challenges, and future perspectives in the clinical implementation of OGM.Please note that manuscripts consisting solely of bioinformatics or computational analysis of public genomic or transcriptomic databases that are not accompanied by validation (independent cohort or biological validation in vitro or in vivo) are out of the scope of this Research Topic. Topic editors: Xinxiu Xu, Stephanie A Hart, Annapoorani Chockalingam, Reena Ray Sisk, Ash Yenamamndra Source: https://www.frontiersin.org/research-topics/81629/chromothripsis-and-copy-number-variation-as-drivers-of-precision-diagnostics-in-lymphoma