Ip Andrew, Della Pia Alexandra, Kim Gee Youn Geeny, Lofters Jason, Behrmann James, Patel Dylon, Kats Simone, Estella Jeffrey Justin, De Dios Ivan, Ma Wanlong, Pecora Andrew L, Goy Andre H, Koprivnikar Jamie, McCloskey James K, Albitar Maher
Hackensack University Medical Center, Oncology, Hackensack, NJ, United States.
John Theurer Cancer Center, Hackensack University Medical Center, Hackensack, NJ, United States.
Front Oncol. 2022 Jun 14;12:923809. doi: 10.3389/fonc.2022.923809. eCollection 2022.
Cytogenetic analysis is important for stratifying patients with various neoplasms. We explored the use of targeted next generation sequencing (NGS) in detecting chromosomal structural abnormalities or copy number variations (CNVs) in patients with myeloid neoplasms.
Plasma cell-free DNA (cfDNA) from 2821 myeloid or lymphoid neoplasm patients were collected. cfDNA was sequenced using a 275 gene panel. CNVkit software was used for analyzing and visualizing CNVs. Cytogenetic data from corresponding bone marrow (BM) samples was available on 89 myeloid samples.
Of the 2821 samples, 1539 (54.5%) showed evidence of mutations consistent with the presence of neoplastic clones in circulation. Of these 1539 samples, 906 (59%) showed abnormalities associated with myeloid neoplasms and 633 (41%) with lymphoid neoplasms. Chromosomal structural abnormalities in cfDNA were detected in 146 (16%) myeloid samples and 76 (12%) lymphoid samples. Upon comparison of the myeloid samples with 89 BM patients, NGS testing was able to reliably detect chromosomal gain or loss, except for fusion abnormalities. When cytogenetic abnormalities were classified according to prognostic classes, there was a complete (100%) concordance between cfDNA NGS data and cytogenetic data.
This data shows that liquid biopsy using targeted NGS is reliable in detecting chromosomal structural abnormalities in myeloid neoplasms. In specific circumstances, targeted NGS may be reliable and efficient to provide adequate information without the need for BM biopsy considering broad mutation profiling can be obtained through adequate sequencing within the same test. Overall, this study supports the use of liquid biopsy for early diagnosis and monitoring of patients with myeloid neoplasms.
细胞遗传学分析对于不同肿瘤患者的分层很重要。我们探索了使用靶向二代测序（NGS）检测髓系肿瘤患者的染色体结构异常或拷贝数变异（CNV）。
收集了2821例髓系或淋巴系肿瘤患者的血浆游离DNA（cfDNA）。使用包含275个基因的基因panel对cfDNA进行测序。CNVkit软件用于分析和可视化CNV。89例髓系样本可获得相应骨髓（BM）样本的细胞遗传学数据。
在2821个样本中，1539个（54.5%）显示出与循环中肿瘤克隆存在一致的突变证据。在这1539个样本中，906个（59%）显示出与髓系肿瘤相关的异常，633个（41%）与淋巴系肿瘤相关。在146个（16%）髓系样本和76个（12%）淋巴系样本中检测到cfDNA中的染色体结构异常。将髓系样本与89例BM患者进行比较时，除融合异常外，NGS检测能够可靠地检测到染色体的增加或减少。当根据预后类别对细胞遗传学异常进行分类时，cfDNA NGS数据与细胞遗传学数据完全（100%）一致。
该数据表明，使用靶向NGS的液体活检在检测髓系肿瘤的染色体结构异常方面是可靠的。在特定情况下，考虑到通过同一检测中的充分测序可获得广泛的突变谱，靶向NGS可能可靠且高效地提供足够信息，而无需进行BM活检。总体而言，本研究支持使用液体活检对髓系肿瘤患者进行早期诊断和监测。
