Genomic instability in individuals with sex determination defects and germ cell cancer.
Journal
Cell death discovery
ISSN: 2058-7716
Titre abrégé: Cell Death Discov
Pays: United States
ID NLM: 101665035
Informations de publication
Date de publication:
23 May 2023
23 May 2023
Historique:
received:
13
03
2023
accepted:
12
05
2023
revised:
28
04
2023
medline:
23
5
2023
pubmed:
23
5
2023
entrez:
22
5
2023
Statut:
epublish
Résumé
The ability to transmit genetic information through generations depends on the preservation of genome integrity. Genetic abnormalities affect cell differentiation, causing tissue specification defects and cancer. We addressed genomic instability in individuals with Differences of Sex Development (DSD), characterized by gonadal dysgenesis, infertility, high susceptibility for different types of cancer, especially Germ Cell Tumors (GCT), and in men with testicular GCTs. Whole proteome analysis of leukocytes, supported by specific gene expression assessment, and dysgenic gonads characterization, uncovered DNA damage phenotypes with altered innate immune response and autophagy. Further examination of DNA damage response revealed a reliance on deltaTP53, which was compromised by mutations in the transactivation domain in DSD-individuals with GCT. Accordingly, drug-induced rescue of DNA damage was achieved by autophagy inhibition but not by stabilization of TP53 in DSD-individuals' blood in vitro. This study elucidates possibilities for prophylactic treatments of DSD-individuals, as well as new diagnostic approaches of GCT.
Identifiants
pubmed: 37217472
doi: 10.1038/s41420-023-01470-6
pii: 10.1038/s41420-023-01470-6
pmc: PMC10202957
doi:
Types de publication
Journal Article
Langues
eng
Pagination
173Informations de copyright
© 2023. The Author(s).
Références
Reprod Biol Endocrinol. 2018 Feb 17;16(1):14
pubmed: 29454353
Proc Natl Acad Sci U S A. 2018 Jul 10;115(28):7398-7403
pubmed: 29946024
Am J Med Genet C Semin Med Genet. 2017 Jun;175(2):304-314
pubmed: 28544305
Eur J Endocrinol. 2021 Jan;184(1):79-88
pubmed: 33112259
Trends Genet. 2023 Mar;39(3):172-174
pubmed: 36496311
Annu Rev Cancer Biol. 2021 Mar;5(1):59-77
pubmed: 34532611
Nature. 1959 Jan 31;183(4657):302-3
pubmed: 13632697
Nat Rev Cancer. 2020 Apr;20(4):203-217
pubmed: 32161398
Lancet Neurol. 2014 Mar;13(3):306-18
pubmed: 24556008
Biomed Res. 2005 Jun;26(3):91-8
pubmed: 16011301
Mol Cell. 2004 May 21;14(4):501-13
pubmed: 15149599
Nature. 1990 Jul 19;346(6281):240-4
pubmed: 1695712
Nat Rev Mol Cell Biol. 2015 Jul;16(7):393-405
pubmed: 26122615
Nat Commun. 2021 Sep 1;12(1):5205
pubmed: 34471128
Autoimmunity. 2015 Mar;48(2):125-8
pubmed: 25295757
Am J Hum Genet. 2018 Aug 2;103(2):261-275
pubmed: 30075113
Sci Rep. 2019 Apr 23;9(1):6460
pubmed: 31015566
Endocrinol Diabetes Metab Case Rep. 2015;2015:150069
pubmed: 26543560
Mod Pathol. 1997 Nov;10(11):1101-5
pubmed: 9388060
Nat Rev Mol Cell Biol. 2016 Jun;17(6):364-78
pubmed: 27165790
Anal Biochem. 1984 Apr;138(1):141-3
pubmed: 6731838
Hum Mol Genet. 2004 Oct 1;13(19):2333-41
pubmed: 15294876
Cell Cycle. 2013 Apr 1;12(7):1022-9
pubmed: 23466706
J Clin Oncol. 2016 Nov 20;34(33):4000-4007
pubmed: 27646943
Cancer Res. 1995 Nov 15;55(22):5187-90
pubmed: 7585571
J Pediatr Adolesc Gynecol. 2020 Feb;33(1):10-14
pubmed: 31465855
Am J Hum Genet. 2022 Dec 1;109(12):2126-2140
pubmed: 36459979
Mol Med Rep. 2020 Jan;21(1):97-106
pubmed: 31746433
Nat Rev Genet. 2017 Nov;18(11):675-689
pubmed: 28804140
Lancet Oncol. 2008 Mar;9(3):239-46
pubmed: 18282803
Semin Cell Dev Biol. 2021 May;113:132-147
pubmed: 33500205
Cancer Cell. 2012 Jun 12;21(6):765-76
pubmed: 22698402
Hum Reprod. 2019 Apr 1;34(4):770-779
pubmed: 30753444
Mutat Res Genet Toxicol Environ Mutagen. 2016 Jan 1;795:36-40
pubmed: 26774665
Endocr Rev. 2006 Aug;27(5):468-84
pubmed: 16735607
Int J Androl. 2007 Aug;30(4):256-63; discussion 263-4
pubmed: 17705807
Nat Immunol. 2013 Jan;14(1):19-26
pubmed: 23238760
Genes Chromosomes Cancer. 1993 Feb;6(2):92-7
pubmed: 7680893
Sci Rep. 2016 Sep 30;6:34220
pubmed: 27687697
Nat Protoc. 2007;2(8):1896-906
pubmed: 17703201
Cell Mol Life Sci. 2009 Feb;66(3):391-406
pubmed: 18854945
Lancet. 1959 Apr 4;1(7075):711-3
pubmed: 13642858
Eur J Biochem. 2001 May;268(10):2764-72
pubmed: 11358490
Sex Dev. 2017;11(5-6):262-268
pubmed: 29197878
Histopathology. 2008 Apr;52(5):644-6
pubmed: 18312345
Cancer Res. 1993 Aug 1;53(15):3574-8
pubmed: 8339263
Commun Biol. 2021 Jul 2;4(1):831
pubmed: 34215848
Sex Dev. 2021;15(5-6):392-410
pubmed: 34634785
Nat Rev Cancer. 2019 Sep;19(9):522-537
pubmed: 31413324
Dev Cell. 2018 Feb 26;44(4):420-431
pubmed: 29486194
Nat Cell Biol. 2017 Jan;19(1):68-75
pubmed: 27918550
Eur J Cancer. 2001 Dec;37(18):2405-12
pubmed: 11720835
Int J Cancer. 2016 Aug 15;139(4):754-8
pubmed: 27061708
Cancers (Basel). 2018 Feb 27;10(3):
pubmed: 29495465
Hum Pathol. 2006 Jan;37(1):101-11
pubmed: 16360422
Clin Endocrinol (Oxf). 2012 Jun;76(6):894-8
pubmed: 22211628
J Immunol. 1982 Jan;128(1):24-9
pubmed: 6274955
Pathol Res Pract. 2020 Nov;216(11):153198
pubmed: 33002849
Cell Immunol. 2015 Apr;294(2):87-94
pubmed: 25708485
J Biol Chem. 2001 Nov 9;276(45):42462-7
pubmed: 11571274
Oncogene. 1999 Nov 4;18(46):6305-12
pubmed: 10597229
Nature. 2019 Jan;565(7741):659-663
pubmed: 30675059
Nature. 2003 Nov 13;426(6963):194-8
pubmed: 14608368
Cell Rep. 2019 Nov 19;29(8):2473-2488.e5
pubmed: 31747614