Abstract
The aims of this systematic review are to refine the catalogue of somatic variants in splenic marginal zone lymphoma (SMZL) and to provide a well-annotated, manually curated database of high-confidence somatic mutations to facilitate variant interpretation for further biological studies and future clinical implementation. Two independent reviewers systematically searched PubMed and Ovid in January 2019 and included studies that sequenced SMZL cases with confirmed diagnosis. The database included fourteen studies, comprising 2817 variants in over 1000 genes from 475 cases. We confirmed the high prevalence of NOTCH2, KLF2 and TP53 mutations and analysis of targeted genes further implicated TNFAIP3, KMT2D, and TRAF3 as recurrent targets of somatic mutation based on their high incidence across studies. The major limitations we encountered were the low number of patients with whole-genome, unbiased analysis and the relative sensitivities of differing sequencing approaches. Overall, we showed that there is little concordance between whole exome sequencing studies of SMZL. We strongly support the continuing unbiased analysis of the SMZL genome for mutations in all protein-coding genes and provide a valuable database resource to facilitate this endeavour that will ultimately improve our understanding of SMZL pathobiology.
Highlights
ObjectivesOur aims were to: a) determine if a systematic review approach would yield novel insight into the genes and pathways targeted by somatic mutations; and b) provide the research community with a unique and accurately annotated database of SMZL mutations, mapped to functionally relevant transcripts in GRch to facilitate future investigations
We chose to perform a systematic review of mutational data from fourteen studies covering three broad categories; 1) discovery WES/WGS studies of SMZL; 2) confirmation/extension of SMZL usually utilizing targeted re-sequencing approaches; and 3) sequencing data drawn from studies of other mature B-cell neoplasm, where SMZL was included as comparison
Our aims were to: a) determine if a systematic review approach would yield novel insight into the genes and pathways targeted by somatic mutations; and b) provide the research community with a unique and accurately annotated database of SMZL mutations, mapped to functionally relevant transcripts in GRch[38] to facilitate future investigations
Summary
Our aims were to: a) determine if a systematic review approach would yield novel insight into the genes and pathways targeted by somatic mutations; and b) provide the research community with a unique and accurately annotated database of SMZL mutations, mapped to functionally relevant transcripts in GRch to facilitate future investigations
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