Common baseline and point of disease progression mutations that are frequent among patients with mantle cell lymphoma (MCL) were discussed in a systematic review and meta-analysis published in Blood Advances.

MCL, an incurable B cell non-Hodgkin lymphoma, has a heterogenous disease course, which can range from indolent to highly aggressive. While some biomarkers are effective for predicting disease course, next-generation genomic sequencing is improving prognostic measurements. Using currently available information about these markers, the MCL International Prognostic Index stratifies patients by risk group, defined as low, medium, and high.

MCL disease course remains difficult to predict, highlighting the need for more reliable genomic particulars, especially as personalized oncology is becoming more viable. This is particularly relevant given the growing understanding around disease and genomic changes caused by anticancer treatment. For this systematic review and meta-analysis, researchers aimed to assess the frequency of genetic mutations in patients with MCL, to examine sequencing and genotyping techniques, and to present the potential clinical significance of these mutations.

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Using 32 articles from 3 databases, investigators were able to review data from 2275 patients with MCL; 164 genes were analyzed and 32 genes were included in the study. Of the cohort, 2127 patients had mutations in 1 or more of the 32 genes, and 2045 patients had baseline samples with genetic mutation information.

At baseline, the probability of mutations in any of the 32 genes was 11.3%. The most frequently mutated gene at baseline was ATM (43.5%), followed by IGH (38.4%), TP53 (26.8%), RB1 (24.3%), and CKD kinase regulators CDKN2A (23.9%) and CCND1 (20.2%).

Fluorescence in situ hybridization (FISH) is mainly used to detect CCND1/IGH fusion for diagnostics in patients with MCL. When exclusing patients who were diagnosed with FISH, 84.6% of the 2127 patients were tested at baseline. This exclusion resulted in a lower overall probability of mutations in the 32 genes (8.8%).

The analysis also noted mutational changes in all genes at a rate of more than 5% difference at baseline vs at disease progression, which included TP53, ATM, KMT2A, MAP3K14, BTK, TRAF2, CHD2, TLR2, ARID2, RIMS2, NOTCH2, TET2, SPEN, NSD2, CARD11, CCND1, SP140, CDKN2A, and S1PR1.

The authors noted that, given the size of the patient sample used, these findings should be seen as a reference for the mutational landscape in MCL, both at baseline and at disease progression after treatment.

“There are significant differences in the frequency of mutations between baseline patient samples and those taken at other clinical milestones such as relapse and progression. These genes should be included in future MCL-specific targeted [next-generation sequencing] panels for further investigation.”


Hill HA, Qi X, Jain P, et al. Genetic mutations and features of mantle cell lymphoma: a systematic review and meta-analysis. Blood Adv. 2020;4(13):2927-2938.