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.
journal_name
Nat Communjournal_title
Nature communicationsauthors
Yurchenko AA,Padioleau I,Matkarimov BT,Soulier J,Sarasin A,Nikolaev Sdoi
10.1038/s41467-020-19633-9subject
Has Abstractpub_date
2020-11-17 00:00:00pages
5834issue
1issn
2041-1723pii
10.1038/s41467-020-19633-9journal_volume
11pub_type
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