XPC deficiency increases risk of hematologic malignancies through mutator phenotype and characteristic mutational signature

Andrey A. Yurchenko, Ismael Padioleau, Bakhyt T. Matkarimov, Jean Soulier, Alain Sarasin and Sergey Nikolaev ()
Additional contact information
Andrey A. Yurchenko: INSERM U981, Gustave Roussy Cancer Campus, Université Paris Saclay
Ismael Padioleau: INSERM U981, Gustave Roussy Cancer Campus, Université Paris Saclay
Bakhyt T. Matkarimov: Nazarbayev University
Jean Soulier: University of Paris, INSERM U944 and CNRS UMR7212, Institut de Recherche Saint-Louis, F-75010
Alain Sarasin: CNRS UMR9019 Genome Integrity and Cancers, Institut Gustave Roussy, Université Paris-Saclay
Sergey Nikolaev: INSERM U981, Gustave Roussy Cancer Campus, Université Paris Saclay

Nature Communications, 2020, vol. 11, issue 1, 1-11

Abstract: Abstract Recent studies demonstrated a dramatically increased risk of leukemia in patients with a rare genetic disorder, Xeroderma Pigmentosum group C (XP-C), characterized by constitutive deficiency of global genome nucleotide excision repair (GG-NER). The genetic mechanisms of non-skin cancers in XP-C patients remain unexplored. In this study, we analyze a unique collection of internal XP-C tumor genomes including 6 leukemias and 2 sarcomas. We observe a specific mutational pattern and an average of 25-fold increase of mutation rates in XP-C versus sporadic leukemia which we presume leads to its elevated incidence and early appearance. We describe a strong mutational asymmetry with respect to transcription and the direction of replication in XP-C tumors suggesting association of mutagenesis with bulky purine DNA lesions of probably endogenous origin. These findings suggest existence of a balance between formation and repair of bulky DNA lesions by GG-NER in human body cells which is disrupted in XP-C patients.

Date: 2020
References: Add references at CitEc
Citations:

Downloads: (external link)
https://www.nature.com/articles/s41467-020-19633-9 Abstract (text/html)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:11:y:2020:i:1:d:10.1038_s41467-020-19633-9

Ordering information: This journal article can be ordered from
https://www.nature.com/ncomms/

DOI: 10.1038/s41467-020-19633-9

Access Statistics for this article

Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie

More articles in Nature Communications from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().