Novel Driver Mutations in GCB Lymphoma Patients That Affect Transcription Factors Binding
Shami-Schnitzer, O.; Tuller, T.
Show abstract
Mutations in the DNA can affect cancer development and progression not only by changing the amino acid chain but also by affecting different regulatory elements such as transcription factors. This study introduces a novel pipeline to identify "mutation blocks" - small genomic areas with high mutation rates that potentially influence transcription factors binding. By analyzing GCB lymphoma patient data, mutations blocks were identified that correlated with gene expression changes and were linked to transcription factor activity. These mutation blocks suggest a selection for mutations that alter gene regulation, contributing to lymphoma development. The analysis identified 56 mutation blocks in germinal center B-cell like diffuse large B-cell lymphoma (GCB DLBCL) patients genomes, affecting genes such as BCL2, MYC, SGK1, and PIM1, and linked to transcription factors including MSC, TCFL5, HOXB7, FOXP3, and ZBTB6. A machine learning model that used gene ontology data suggested further potential transcription factors-gene pairs influencing cancer. These findings highlight the role of synonymous and silent mutations in altering transcription factors binding and gene expression, offering insights into the mechanisms of GCB lymphoma.
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