XPC deficiency increases risk of hematologic malignancies through mutator phenotype and characteristic mutational signature.
Journal
Nature communications
ISSN: 2041-1723
Titre abrégé: Nat Commun
Pays: England
ID NLM: 101528555
Informations de publication
Date de publication:
17 11 2020
17 11 2020
Historique:
received:
19
03
2020
accepted:
07
10
2020
entrez:
18
11
2020
pubmed:
19
11
2020
medline:
17
12
2020
Statut:
epublish
Résumé
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.
Identifiants
pubmed: 33203900
doi: 10.1038/s41467-020-19633-9
pii: 10.1038/s41467-020-19633-9
pmc: PMC7672101
doi:
Substances chimiques
DNA-Binding Proteins
0
XPC protein, human
156533-34-5
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
5834Références
J Mol Biol. 2001 Sep 14;312(2):335-46
pubmed: 11554790
Genome Res. 2016 Feb;26(2):174-82
pubmed: 26755635
Cell Rep. 2014 Nov 20;9(4):1228-34
pubmed: 25456125
Anaesth Intensive Care. 2014 May;42(3):310-4
pubmed: 24794469
Bioinformatics. 2012 Oct 1;28(19):2520-2
pubmed: 22908215
N Engl J Med. 2016 Jun 9;374(23):2209-2221
pubmed: 27276561
Curr Protoc Bioinformatics. 2014 Sep 08;47:11.12.1-34
pubmed: 25199790
DNA Repair (Amst). 2011 Jun 10;10(6):577-85
pubmed: 21482201
Hum Gene Ther. 2003 Jul 1;14(10):983-96
pubmed: 12869216
BMC Bioinformatics. 2019 Sep 2;20(1):450
pubmed: 31477009
Nucleic Acids Res. 2016 Sep 19;44(16):e131
pubmed: 27270079
Bioinformatics. 2009 Jul 15;25(14):1754-60
pubmed: 19451168
BMC Genomics. 2019 Aug 30;20(1):685
pubmed: 31470794
Arch Dermatol. 1987 Feb;123(2):241-50
pubmed: 3545087
Cell Cycle. 2011 Jul 15;10(14):2276-80
pubmed: 21701262
Bioinformatics. 2012 Jul 15;28(14):1919-20
pubmed: 22576172
Genome Res. 2007 Jun;17(6):917-27
pubmed: 17568007
Oncogene. 2005 Jan 13;24(3):469-78
pubmed: 15558025
Bioinformatics. 2018 Jan 15;34(2):330-337
pubmed: 29028923
Bioinformatics. 2008 Dec 1;24(23):2684-90
pubmed: 18852176
Cell Rep. 2013 Jan 31;3(1):246-59
pubmed: 23318258
Arch Dermatol. 1994 Aug;130(8):1018-21
pubmed: 8053698
Genet Med. 2018 Oct;20(10):1196-1205
pubmed: 29388947
Orphanet J Rare Dis. 2011 Nov 01;6:70
pubmed: 22044607
Genome Biol. 2018 Jul 24;19(1):95
pubmed: 30041675
Bioinformatics. 2018 Mar 1;34(5):867-868
pubmed: 29096012
Oncogene. 2000 Oct 12;19(43):5034-7
pubmed: 11042691
Nature. 2015 Feb 19;518(7539):317-30
pubmed: 25693563
N Engl J Med. 2013 May 30;368(22):2059-74
pubmed: 23634996
Nature. 2018 Mar 15;555(7696):371-376
pubmed: 29489755
Sci Rep. 2017 Sep 6;7(1):10660
pubmed: 28878254
Nat Genet. 2011 May;43(5):491-8
pubmed: 21478889
Br J Dermatol. 2013 Dec;169(6):1279-87
pubmed: 23889214
Bioinformatics. 2016 Oct 1;32(19):3047-8
pubmed: 27312411
Proc Natl Acad Sci U S A. 2010 Jan 5;107(1):139-44
pubmed: 19966280
PLoS One. 2012;7(1):e30377
pubmed: 22276185
Br J Dermatol. 2016 Feb;174(2):439-43
pubmed: 26211814
J Invest Dermatol. 2010 Jun;130(6):1537-42
pubmed: 20054342
Genome Res. 2002 Jun;12(6):996-1006
pubmed: 12045153
Br J Dermatol. 2013 May;168(5):1109-13
pubmed: 23278166
Genome Med. 2018 Apr 25;10(1):33
pubmed: 29695279
Nat Genet. 2019 Jan;51(1):36-41
pubmed: 30510240
Science. 2017 Mar 24;355(6331):1330-1334
pubmed: 28336671
Nucleic Acids Res. 2019 Jan 8;47(D1):D766-D773
pubmed: 30357393
Cell. 2016 Jan 28;164(3):538-49
pubmed: 26806129
Hum Mutat. 2015 Apr;36(4):E2423-9
pubmed: 25703262
Nat Commun. 2016 Jan 11;7:10208
pubmed: 26751768
Lancet Oncol. 2018 Jun;19(6):785-798
pubmed: 29753700
Nature. 2013 Aug 22;500(7463):415-21
pubmed: 23945592
Haematologica. 2020 Apr;105(4):e144-e146
pubmed: 31439674
J Med Genet. 2011 Mar;48(3):168-76
pubmed: 21097776
Bioinformatics. 2009 Aug 15;25(16):2078-9
pubmed: 19505943
Blood. 2019 Jun 20;133(25):2718-2724
pubmed: 30914417
Cancer Res. 2008 Mar 1;68(5):1347-53
pubmed: 18316597
Br J Dermatol. 1992 Nov;127(5):485-91
pubmed: 1281671
DNA Repair (Amst). 2013 Dec;12(12):1081-6
pubmed: 24084170
Genome Res. 2019 Jul;29(7):1067-1077
pubmed: 31221724
Environ Mol Mutagen. 2012 Dec;53(9):777-86
pubmed: 22965922