Circulating Tumor DNA: Less Invasive, More Representative Method to Unveil the Genomic Landscape of Newly Diagnosed Multiple Myeloma Than Bone Marrow Aspirates.
Circulating Tumor DNA: Less Invasive, More Representative Method to Unveil the Genomic Landscape of Newly Diagnosed Multiple Myeloma Than Bone Marrow Aspirates.
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循环肿瘤 DNA：与骨髓抽吸相比，侵入性更小、更具代表性的方法能够揭示新诊断的多发性骨髓瘤的基因组图谱
作者：
简单总结 多发性骨髓瘤恶性浆细胞DNA基因组学研究是一个热门话题，主要基于单位骨髓穿刺。在这项研究中，我们表明，在新诊断的多发性骨髓瘤中，循环肿瘤 DNA 靶向下一代测序分析揭示了比骨髓抽吸物更全面的基因组结构。转录调控途径和DNA修复途径中的循环肿瘤DNA突变是无进展生存的独立预测因素。 ctDNA 改变与新诊断的多发性骨髓瘤的预后和治疗反应相关。摘要 多发性骨髓瘤（MM）的基因组异常具有高度异质性和动态性。捕获这些改变的代表性图像对于了解疾病的分子发病机制和进展至关重要，但受到基于单点侵入性骨髓（BM）活检的基因组学研究的限制。我们比较了 82 名新诊断 MM 患者的循环肿瘤 DNA (ctDNA) 和 BM 的突变情况。测序中使用了 413 个基因组。我们的结果显示，超过 70% 的 MM 患者表现出一种或多种具有体细胞突变的基因，并且至少一半的突变基因在 ctDNA 和 BM 样本之间共享。与BM样本相比，ctDNA在共享驱动基因中表现出更多类型的驱动突变、更多数量的独特突变基因和亚克隆簇、更多的易位相关突变以及转录调控途径中富集的突变基因的频率更高。多变量 Cox 分析显示，年龄、转录调控途径和 DNA 修复途径中的 ctDNA 突变是无进展生存期 (PFS) 的独立预测因子。我们的结果表明，ctDNA 测序提供了有关基因组不稳定性的更全面信息，并且是风险分层和新诊断 MM 中比骨髓具有潜在代表性的生物标志物。
Simple Summary The study of malignant plasma cell DNA genomics in multiple myeloma is a hot topic, which is mainly based on one-site bone marrow aspirates. In this study, we showed that circulating tumor DNA targeted next-generation sequencing analysis revealed a more comprehensive genomic architecture than bone marrow aspirates in newly diagnosed multiple myeloma. Circulating tumor DNA mutation in the transcriptional regulation pathway and DNA repair pathway were independent predictors of progression-free survival. ctDNA alterations correlated with prognosis and therapy response in newly diagnosed multiple myeloma. Abstract Multiple myeloma (MM) is highly heterogenous and dynamic in its genomic abnormalities. Capturing a representative image of these alterations is essential in understanding the molecular pathogenesis and progression of the disease but was limited by single-site invasive bone marrow (BM) biopsy-based genomics studies. We compared the mutational landscapes of circulating tumor DNA (ctDNA) and BM in 82 patients with newly diagnosed MM. A 413-gene panel was used in the sequencing. Our results showed that more than 70% of MM patients showed one or more genes with somatic mutations and at least half of the mutated genes were shared between ctDNA and BM samples. Compared to the BM samples, ctDNA exhibited more types of driver mutations in the shared driver genes, higher numbers of uniquely mutated genes and subclonal clusters, more translocation-associated mutations, and higher frequencies of mutated genes enriched in the transcriptional regulation pathway. Multivariate Cox analysis showed that age, ctDNA mutations in the transcriptional regulation pathway and DNA repair pathway were independent predictors of progression-free survival (PFS). Our results demonstrated sequencing of ctDNA provides more thorough information on the genomic instability and is a potential representative biomarker for risk stratification and in newly diagnosed MM than bone marrow.
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影响因子：
16.6
作者：
Kis O;Kaedbey R;Chow S;Danesh A;Dowar M;Li T;Li Z;Liu J;Mansour M;Masih-Khan E;Zhang T;Bratman SV;Oza AM;Kamel-Reid S;Trudel S;Pugh TJ
通讯作者：
Pugh TJ
影响因子：
45.3
作者：
Bertamini, Luca;Oliva, Stefania;Gay, Francesca
通讯作者：
Gay, Francesca
DOI：
10.1016/j.beha.2021.101329
发表时间：
2021-12
期刊：
Best practice & research. Clinical haematology
影响因子：
--
作者：
Montefiori LE;Mullighan CG
通讯作者：
Mullighan CG
影响因子：
5.8
作者：
Li, Jason;Lupat, Richard;Gorringe, Kylie L.
通讯作者：
Gorringe, Kylie L.
影响因子：
11.4
作者：
Guo G;Raje NS;Seifer C;Kloeber J;Isenhart R;Ha G;Yee AJ;O'Donnell EK;Tai YT;Richardson PG;Bianchi G;Laubach JP;Warren D;Gemme E;Voisine J;Frede J;Kokkalis A;Yun H;Dimitrova V;Vijaykumar T;Meyerson M;Munshi NC;Anderson KC;Knoechel B;Lohr JG
通讯作者：
Lohr JG