Background/Objectives:Accurate detection of all classes of genomic structural variants (SVs), including chromosomal rearrangements and copy number alterations (CNAs), is essential for the diagnosis and classification of hematologic neoplasms. Conventional cytogenetic methods currently serve as routine clinical tools for detecting SVs. However, each commonly used cytogenetic test has specific limitations, and sequential application of these different tests may delay timely diagnosis and treatment.Methods: In this study, we evaluated the feasibility and utility of genomic proximity mapping (GPM), a novel high-throughput chromosome conformation capture (Hi-C)-based next-generation sequencing (NGS) method, to identify chromosomal and genetic aberrations in hematologic neoplasms in the clinical setting. GPM was performed on 18 cases of hematologic neoplasms (fresh/frozen cells or formalin-fixed paraffin-embedded tissue), and concordance with other methodologies was assessed, including karyotyping, FISH, RT-PCR, chromosomal microarray analysis (CMA), and/or RNA sequencing.Results:GPM reliably detected balanced and unbalanced chromosomal rearrangements, including chimeric gene fusions and gene juxtapositions, with 95.2% concordance with previously applied methods in cases with >10% tumor burden. Additionally, GPM can detect CNAs and copy-neutral loss of heterozygosity (cnLOH) simultaneously in a single assay. Furthermore, detection of genomic rearrangements not identified by other methods improved the accuracy of disease classification.Conclusions:These findings demonstrate that GPM is a powerful method for identifying clinically actionable variants in hematologic neoplasms, overcoming some limitations of current cytogenetic technologies and improving the diagnostic accuracy and classification in challenging cases
背景/目的：准确检测所有类型的基因组结构变异（SVs），包括染色体重排和拷贝数变异（CNAs），对于血液肿瘤的诊断和分类至关重要。目前，常规细胞遗传学方法作为检测SVs的临床常规工具。然而，每种常用的细胞遗传学检测方法都有其特定的局限性，并且这些不同检测方法的顺序应用可能会延误及时诊断和治疗。 方法：在本研究中，我们评估了基因组邻近定位（GPM）在临床环境中识别血液肿瘤染色体和遗传异常的可行性和实用性。GPM是一种基于高通量染色体构象捕获（Hi-C）的新型下一代测序（NGS）方法。我们对18例血液肿瘤（新鲜/冷冻细胞或福尔马林固定石蜡包埋组织）进行了GPM检测，并评估了其与其他方法（包括核型分析、荧光原位杂交、逆转录聚合酶链反应、染色体微阵列分析和/或RNA测序）的一致性。 结果：GPM可靠地检测了平衡和不平衡染色体重排，包括嵌合基因融合和基因并置，在肿瘤负荷大于10%的病例中，与先前应用的方法一致性达到95.2%。此外，GPM可以在单次检测中同时检测CNAs和拷贝数中性杂合性缺失（cnLOH）。更重要的是，GPM检测到了其他方法未发现的基因组重排，从而提高了疾病分类的准确性。 结论：这些发现表明，GPM是一种强大的方法，可用于识别血液肿瘤中具有临床可操作性的变异，克服了当前细胞遗传学技术的某些局限性，并在具有挑战性的病例中提高了诊断准确性和分类能力。
肿瘤(癌症)患者之家