Genomic signatures in plasma circulating tumor DNA reveal treatment response and prognostic insights in mantel cell lymphoma

作者：Zhou Ouyang, Ruolan Zeng, Song Wang, Xiaoying Wu, Yajun Li, Yizi He, Caiqin Wang, Xia Chen, Qiuxiang Ou, Hua Bao, Wei Yang, Ling Xiao, Hui Zhou · 发表于：Cancer Cell International · 年份：2025 · DOI：10.1186/s12935-025-03789-9 · 被引用次数：4 · 研究领域：Lymphoma Diagnosis and Treatment、Cancer Genomics and Diagnostics、Genetic factors in colorectal cancer

BACKGROUND: Mantle cell lymphoma (MCL) is an aggressive subtype of B-cell non-Hodgkin's lymphoma. The applicability of circulating tumor DNA (ctDNA) for predicting treatment response and prognosis in MCL remains underexplored. METHODS: This study included 34 MCL patients receiving first-line chemoimmunotherapy. We assessed the ability of plasma ctDNA to detect tumor-specific genetic alterations and explored its potential as a noninvasive biomarker for treatment response and prognosis in MCL. RESULTS: Commonly mutated genes in MCL included CCND1 (93.5%), ATM (48.4%), KMT2D (25.8%), and TP53 (25.8%). Subgroup analysis of tissue samples showed that CDKN2A mutations (P = 0.028), along with alterations in BCR and TCR signaling (P = 0.004) and the PI3K pathway (P = 0.008), were enriched in the blastoid subtype. ATM mutations (P = 0.041) were more prevalent in MIPI-low patients, while epigenetic chromatin remodeling pathway alterations (P = 0.028) were more common in MIPI-high patients. Plasma ctDNA demonstrated high sensitivity for detecting structural variants (96.6%), followed by mutations (71.3%) and copy number variants (30.0%). 75% of patients exhibited moderate-to-high concordance in detecting genomic variants between plasma and tissue samples. Pretreatment ctDNA levels exhibited high specificity in predicting clinical efficacy but had a suboptimal sensitivity of 68.2%. Higher ctDNA levels were significantly associated with shorter progression-free survival (PFS; P = 0.002) a...