KMT2D - morinlab/LLMPP GitHub Wiki

bibliography: 'morinlab.bib' csl: 'NLM.csl' link-citations: true nocite: | @rossiCodingGenomeSplenic2012, @deschGenotypingCirculatingTumor2020, @morinFrequentMutationHistonemodifying2011, @beaLandscapeSomaticMutations2013

Overview

KMT2D (also known as MLL2) encodes a histone H3K4 methyltransferase, playing a crucial role in germinal center B cell development and function. Mutations in KMT2D are among the most common mutations in FL and are also common in DLBCL.[@morinFrequentMutationHistonemodifying2011] KMT2D mutations are recurrent but less common in BL and MCL and many other B-cell neoplasms. Mutations typically cause loss of KMT2D function, leading to diminished H3K4 methylation, impacting gene expression that favours lymphomagenesis. KMT2D mutations are associated with poor prognosis in DLBCL.[@deschGenotypingCirculatingTumor2020; @morinFrequentMutationHistonemodifying2011]

First identified as mutated in DLBCL and FL in 2011 by Morin et al.[@morinFrequentMutationHistonemodifying2011] Mutations were later described in MCL in 2013 by Bea et al.[@beaLandscapeSomaticMutations2013] KMT2D mutations were later reported in BL by Grande et al.[@grandeGenomewideDiscoverySomatic2019]

Experimental Evidence

Driver mutations affecting this gene in BL/DLBCL/FL have been experimentally demonstrated to cause a reduction or loss of function (LOF).[@zhangDisruptionKMT2DPerturbs2015]