长读长测序与Hi-C技术相结合以识别癌症中的染色体畸变事件

Combination of Long-Read Sequencing and Hi-C Technology to Identify Chromoanagenesis Events in Cancer.

作者信息

Klever Marius-Konstantin, Jungnitsch Julius, Bullinger Lars

机构信息

Division of Hematology, Oncology, and Cancer Immunology, Medical Department, Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Berlin, Germany.

Department of Clinical Immunology, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark.

出版信息

Methods Mol Biol. 2025;2968:161-172. doi: 10.1007/978-1-0716-4750-9_9.

DOI:10.1007/978-1-0716-4750-9_9

PMID:40884643

Abstract

Structural variants are of major importance in cancer genetics. Especially when it comes to the detection of complex structural variants as in chromoanagenesis, detection tools like array-CGH, karyotyping, or even whole-genome sequencing do not provide the necessary resolution and/or accuracy. Here, we present a novel structural variant (SV) detection workflow that integrates genomic DNA (gDNA) long-read sequencing and Hi-C sequencing. With this workflow, high-confident SV calling at very high resolution can be archived. Applying it to a cohort of acute myeloid leukemia (AML) with a complex karyotype led to new insights about the actual complexity of chromoanagenesis and can enhance subsequent functional studies of the underlying pathomechanisms.

摘要

结构变异在癌症遗传学中至关重要。尤其是在检测诸如染色体混乱等复杂结构变异时，像阵列比较基因组杂交（array-CGH）、核型分析甚至全基因组测序等检测工具都无法提供所需的分辨率和/或准确性。在此，我们提出了一种新型的结构变异（SV）检测工作流程，该流程整合了基因组DNA（gDNA）长读长测序和Hi-C测序。通过此工作流程，可以实现高分辨率下的高置信度SV检测。将其应用于一组具有复杂核型的急性髓系白血病（AML）患者，可对染色体混乱的实际复杂性产生新的见解，并能加强对潜在发病机制的后续功能研究。