SETD2 Haploinsufficiency Enhances Germinal Center-Associated AICDA Somatic Hypermutation to Drive B-cell Lymphomagenesis.

Wilfred Leung Matthew R TeaterCeyda DurmazCem Meydan Alexandra G Chivu Amy ChadburnEdward J RiceAshlesha MuleyJeannie M Camarillo Jaison ArivalaganZiyi LiChristopher R FlowersMichael P SnyderCharles G DankoMarcin ImielinskiSandeep S DaveScott A Armstrong Christopher E Mason Ari M Melnick

Published in: Cancer discovery (2022)

Our findings define a B cell-specific oncogenic effect of SETD2 heterozygous mutation, which unleashes AICDA mutagenesis of nontemplate strand DNA in the GC reaction, resulting in lymphomas with heavy mutational burden. GC-derived lymphomas did not tolerate SETD2 homozygous deletion, pointing to a novel context-specific therapeutic vulnerability. This article is highlighted in the In This Issue feature, p. 1599.

Keyphrases

crispr cas
machine learning
climate change
early onset
deep learning
gas chromatography
single molecule
gene expression
mass spectrometry
high resolution
dna methylation
circulating tumor cells
neural network
tandem mass spectrometry