A broad atlas of somatic hypermutation allows prediction of activation-induced deaminase targets

Ángel F. Álvarez-Prado, Pablo Pérez-Durán, Arantxa Pérez-García, Alberto Benguria, Carlos Torroja, Virginia G. de Yébenes, Almudena R. Ramiro*

*Corresponding author for this work

Research output: Contribution to journalArticleResearchpeer-review

68 Citations (Scopus)

Abstract

Activation-induced deaminase (AID) initiates antibody diversification in germinal center (GC) B cells through the deamination of cytosines on immunoglobulin genes. AID can also target other regions in the genome, triggering mutations or chromosome translocations, with major implications for oncogenic transformation. However, understanding the specificity of AID has proved extremely challenging. We have sequenced at very high depth > 1,500 genomic regions from GC B cells and identified 275 genes targeted by AID, including 30 of the previously known 35 AID targets. We have also identified the most highly mutated hotspot for AID activity described to date. Furthermore, integrative analysis of the molecular features of mutated genes coupled to machine learning has produced a powerful predictive tool for AID targets. We also have found that base excision repair and mismatch repair back up each other to faithfully repair AID-induced lesions. Finally, our data establish a novel link between AID mutagenic activity and lymphomagenesis.

Original languageEnglish
Pages (from-to)761-771
Number of pages11
JournalJournal of Experimental Medicine
Volume215
Issue number3
DOIs
Publication statusPublished - 1 Mar 2018
Externally publishedYes

Fingerprint

Dive into the research topics of 'A broad atlas of somatic hypermutation allows prediction of activation-induced deaminase targets'. Together they form a unique fingerprint.

Cite this