What is it about?
We integrated hundreds of exomes and whole-genomes from B-cell lymphoma and Chronic Lymphocitic Leukemia (CLL) patients into a single analysis. Using new bioinformatic tools, we were able to construct the landscape of mutational drivers in B-cell tumors, pointing towards dozens of recurrently mutated genes and derregulated pathways. This information provides a better understanding of lymphoma biology, and can be used to develop new targeted therapies aiming to disrupt the aberrant activation of some pathways in lymphomagenesis.
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Why is it important?
I believe this is an important analysis because it is the first of its class exclusively dedicated to B-cell tumors. These tumors are very heterogeneous in their clinical presentation, but all arise from B-cells in different stages of maturation. The results translated into the discovery of new potential drug targets (e.g., DTX-1), aberrantions involving immune check-point regulators (CD83), and the skewed distribution of muations in tyrosine kinase genes (e.g., SGK-1) in aggresive lymphomas compared with low-grade tumors. Finally, we could also detect recurrent mutations in interleukin genes and their receptors, which probably indicate a functional role in autocrine singalling during lymphoma development and progression.
Perspectives
I personally found this analysis relevant due to various issues. Firstly, pan-tumor analysis were previously performed, but they mostly excluded lymhoid neoplasms, so a general overview of the genomic determinats of this disease was pending to be performed. Secondly, we need to better indentify recurrently disrupted genes and pathways, as these can be used to direct new targeted therapies and to develop novel immunotherapies. Finally, the present analysis also identified differential events between agressive and low-grade lymphomas, which point towards a key role of some genes in the malignant evolution of these disorders (e.g., potential drug targets). The results of this analysis provide a general overview of the altered pathways in B-cell lymhomagenesis, and these can support the activity of many researchers working of the filed.
Adrián Mosquera Orgueira
Read the Original
This page is a summary of: Detection of new drivers of frequent B-cell lymphoid neoplasms using an integrated analysis of whole genomes, PLoS ONE, May 2021, PLOS,
DOI: 10.1371/journal.pone.0248886.
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