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Targets and consequences of activation-induced cytidine deaminase-mediated mutagenesis in tumours

Project goals

Activation-induced cytidine deaminase (AID) causes mutations in immunoglobulin genes of activated B cells and is required for the production of high-affinity antibodies. However, AID also causes mutations in non-immunoglobulin genes, contributing to the development of tumours. Histone genes are frequent targets of AID activity, both in human lymphomas and in murine cell models. The role of histone genes in tumour development has been increasingly studied recently. In this project, I analyse the extent, type, and consequences of mutagenesis of histone genes and their regulatory regions by AID and the possibility of using mutations in histone genes to detect AID activity in different types of tumours.

Keywords

cancerlymphomaactivation-induced cytidine deaminasehypermutationmutational signatureshistones

Public support

  • Provider

    Czech Science Foundation

  • Programme

    —

  • Call for proposals

    SGA0202400004

  • Main participants

    Univerzita Karlova / 1. lékařská fakulta

  • Contest type

    VS - Public tender

  • Contract ID

    24-11338I

Alternative language

  • Project name in Czech

    Cíle a důsledky mutageneze prostřednictvím aktivací indukované cytidin deaminázy v nádorech

  • Annotation in Czech

    Aktivací indukovaná cytidin deamináza (AID) způsobuje mutace v imunoglobulinových genech aktivovaných B buněk a je nezbytná pro vznik protilátek s vysokou afinitou k antigenu. AID však také způsobuje mutace mimo imunoglobulinové geny a přispívá tak ke vzniku nádorů. Častým cílem aktivity AID jsou histonové geny, a to jak v lidských lymfomech, tak v myších buněčných modelech. Role histonových genů v nádorech se v poslední době čím dál více studuje. V tomto projektu analyzuji rozsah, typ a důsledky mutageneze histonových genů a jejich regulačních oblastí vlivem AID a možnost jejich využití pro detekci aktivity AID v různých typech nádorů.

Scientific branches

  • R&D category

    ZV - Basic research

  • OECD FORD - main branch

    10601 - Cell biology

  • OECD FORD - secondary branch

    10608 - Biochemistry and molecular biology

  • OECD FORD - another secondary branch

    —

  • CE - Biochemistry
    EA - Morphology and cytology
    EB - Genetics and molecular biology

Solution timeline

  • Realization period - beginning

    Mar 1, 2024

  • Realization period - end

    Dec 31, 2027

  • Project status

    B - Running multi-year project

  • Latest support payment

    Mar 28, 2024

Data delivery to CEP

  • Confidentiality

    S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

  • Data delivery code

    CEP25-GA0-GN-R

  • Data delivery date

    Feb 21, 2025

Finance

  • Total approved costs

    6,323 thou. CZK

  • Public financial support

    6,323 thou. CZK

  • Other public sources

    0 thou. CZK

  • Non public and foreign sources

    0 thou. CZK

Basic information

Recognised costs

6 323 CZK thou.

Public support

6 323 CZK thou.

100%

Provider

Czech Science Foundation

OECD FORD

Cell biology

Solution period

01. 03. 2024 - 31. 12. 2027

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