Pan-cancer landscape of AID-related mutations, composite mutations, and their potential role in the ICI response.
Journal
NPJ precision oncology
ISSN: 2397-768X
Titre abrégé: NPJ Precis Oncol
Pays: England
ID NLM: 101708166
Informations de publication
Date de publication:
01 Dec 2022
01 Dec 2022
Historique:
received:
26
05
2022
accepted:
02
11
2022
entrez:
1
12
2022
pubmed:
2
12
2022
medline:
2
12
2022
Statut:
epublish
Résumé
Activation-induced cytidine deaminase, AICDA or AID, is a driver of somatic hypermutation and class-switch recombination in immunoglobulins. In addition, this deaminase belonging to the APOBEC family may have off-target effects genome-wide, but its effects at pan-cancer level are not well elucidated. Here, we used different pan-cancer datasets, totaling more than 50,000 samples analyzed by whole-genome, whole-exome, or targeted sequencing. AID mutations are present at pan-cancer level with higher frequency in hematological cancers and higher presence at transcriptionally active TAD domains. AID synergizes initial hotspot mutations by a second composite mutation. AID mutational load was found to be independently associated with a favorable outcome in immune-checkpoint inhibitors (ICI) treated patients across cancers after analyzing 2000 samples. Finally, we found that AID-related neoepitopes, resulting from mutations at more frequent hotspots if compared to other mutational signatures, enhance CXCL13/CCR5 expression, immunogenicity, and T-cell exhaustion, which may increase ICI sensitivity.
Identifiants
pubmed: 36456685
doi: 10.1038/s41698-022-00331-2
pii: 10.1038/s41698-022-00331-2
pmc: PMC9715662
doi:
Types de publication
Journal Article
Langues
eng
Pagination
89Subventions
Organisme : Institut National Du Cancer (French National Cancer Institute)
ID : SiRIC CURAMUS
Organisme : Institut National Du Cancer (French National Cancer Institute)
ID : SIRIC CURAMUS
Organisme : Institut National Du Cancer (French National Cancer Institute)
ID : SIRIC CURAMUS
Organisme : Institut National Du Cancer (French National Cancer Institute)
ID : SIRIC CURAMUS
Organisme : Institut National Du Cancer (French National Cancer Institute)
ID : SIRIC CURAMUS
Organisme : Institut National Du Cancer (French National Cancer Institute)
ID : SIRIC CURAMUS
Organisme : Agence Nationale de la Recherche (French National Research Agency)
ID : ANR-10-IAIHU-06
Informations de copyright
© 2022. The Author(s).
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