Mutational and copy number analysis at diagnosis and relapse of mantle cell lymphoma

作者：Erel Joffe, Manik Uppal, Serena Zheng, Kurt S. Bantilan, Connie Lee Batlevi, Zachary D. Epstein‐Peterson, Paola Ghione, Paul A. Hamlin, Matthew J. Matasar, Alison J. Moskowitz, Ariela Noy, M. Lia Palomba, Gotfried Von Keudell, Lorenzo Falchi, Joachim Yahalom, Vitaly Segodin, Nikita Kotlov, Evgeniy E. Egorov, Sandrine Degryse, Aleksander Bagaev, Nathan Fowler, Maria E. Arcila, Ahmet Doǧan, Gilles Salles, Anita Kumar, Andrew D. Zelenetz · 发表于：Haematologica · 年份：2025 · DOI：10.3324/haematol.2024.286813 · 被引用次数：1 · 研究领域：Lymphoma Diagnosis and Treatment、Cancer Genomics and Diagnostics、Genetic factors in colorectal cancer

Most patients diagnosed with mantle cell lymphoma (MCL) experience extended remissions following frontline chemoimmunotherapy, yet with with extended follow-up, relapses seem nearly inevitable. This study aimed to define the genomic landscape of MCL at diagnosis and relapse and investigate the clonal evolutionary dynamics associated with progression of disease (POD). We conducted comprehensive genomic sequencing on 214 tumor specimens from 189 patients, including 144 treatment-naïve and 70 POD samples, with 25 patients providing longitudinal paired samples pre-treatment and at POD. Comparative analyses were performed on single nucleotide variants (SNVs), insertions/deletions (indels), and copy number alterations (CNAs) to assess genomic differences between treatment-naïve and relapsed specimens. Additionally, mutational signatures were evaluated in pre-treatment samples, stratified by time to progression (≤24 months vs. >24 months). One hundred patients who received standard frontline chemoimmunotherapy were included in the survival analysis. Genomic profiles of pre-treatment specimens from patients who ultimately relapsed were strikingly similar to those observed in POD, while distinctly different from profiles associated with prolonged remissions. This genomic 'stability' was further confirmed by analysis of 25 paired specimens, demonstrating a remarkable genomic concordance despite extended remission periods (median >3 years), without a clear pattern of acquired alteration...