Zhao Davidson, Lang Noémie, Liu Ting, Shelton Victoria, Rangel-Patiño Juan, Gong Inna Y, Hong Michael, Travas Anthea, Murad Vanessa, Alrekhais Ibrahim, Metser Ur, Prica Anca, Kukreti Vishal, Bhella Sita, Vijenthira Abi, Crump Michael, Kuruvilla John, Arruda Andrea, Minden Mark D, Lam Bernard, Kridel Robert
Princess Margaret Cancer Centre-University Health Network, Toronto, Canada.
Department of Medical Biophysics, University of Toronto, Toronto, Canada.
JCO Precis Oncol. 2025 Jul;9:e2500200. doi: 10.1200/PO-25-00200. Epub 2025 Jul 9.
Although deep targeted DNA sequencing of liquid biopsies has shown prognostic utility in large B-cell lymphoma (LBCL), the routine clinical adoption of these assays remains limited because of their high costs.
Here, leveraging a well-annotated cohort encompassing both frontline and relapsed/refractory (R/R) LBCL, we profiled patient plasma samples with two complementary modalities-ultra-low-pass whole-genome sequencing (ULP-WGS) and deep targeted DNA sequencing, the former being a cost-effective method to profile large scale chromosomal abnormalities and estimate tumor burden.
Our findings revealed a strong association of high cell-free tumor burden by both genomic profiling modalities with established measures of tumor burden and patient survival. Notably, the associations with survival remained statistically significant after accounting for international prognostic index scoring. Furthermore, we showed that del(17p) in circulating tumor DNA as detected by ULP-WGS was strongly associated with mutation status and predicted for significantly inferior outcome in frontline LBCL patients but not in patients with R/R LBCL.
Our study demonstrates that ULP-WGS can provide robust prognostic biomarkers for both frontline and R/R LBCL, highlighting its broad applicability for risk stratification.
尽管液体活检的深度靶向DNA测序已在大B细胞淋巴瘤（LBCL）中显示出预后价值，但由于成本高昂，这些检测方法在临床常规应用中仍然有限。
在此，我们利用一个涵盖一线和复发/难治性（R/R）LBCL的注释完善的队列，采用两种互补方法对患者血浆样本进行分析——超低通量全基因组测序（ULP-WGS）和深度靶向DNA测序，前者是一种经济有效的方法，可用于分析大规模染色体异常并估计肿瘤负荷。
我们的研究结果显示，两种基因组分析方法所检测到的高游离肿瘤负荷与既定的肿瘤负荷指标和患者生存率密切相关。值得注意的是，在考虑国际预后指数评分后，与生存率的相关性仍具有统计学意义。此外，我们还表明，ULP-WGS检测到的循环肿瘤DNA中的del(17p)与 突变状态密切相关，并预测一线LBCL患者的预后明显较差，但R/R LBCL患者并非如此。
我们的研究表明，ULP-WGS可为一线和R/R LBCL提供可靠的预后生物标志物，突出了其在风险分层中的广泛适用性。
