Identification and characterization of ATM founder mutation in BRCA-negative breast cancer patients of Arab ethnicity.
Journal
Scientific reports
ISSN: 2045-2322
Titre abrégé: Sci Rep
Pays: England
ID NLM: 101563288
Informations de publication
Date de publication:
27 Nov 2023
27 Nov 2023
Historique:
received:
04
09
2023
accepted:
23
11
2023
medline:
30
11
2023
pubmed:
29
11
2023
entrez:
28
11
2023
Statut:
epublish
Résumé
Breast cancer (BC) is the most prevalent malignancy among women worldwide with germline pathogenic variants/likely pathogenic variants (PVs/LPVs) in BRCA1/2 accounting for a large portion of hereditary cases. Recently, heterozygous PVs/LPVs in the ATM serine/threonine kinase or Ataxia-telangiectasia mutated gene (ATM) has been identified as a moderate susceptibility factor for BC in diverse ethnicities. However, the prevalence of ATM PVs/LPVs in BC susceptibility in Arab populations remains largely unexplored. This study investigated the prevalence of ATM PVs/LPVs among BC patients from Saudi Arabia, employing capture-sequencing technology for ATM PVs/LPVs screening in a cohort of 715 unselected BC patients without BRCA1/2 PVs/LPVs. In addition, founder mutation analysis was conducted using the PHASE program. In our entire cohort, four unique PVs/LPVs in the ATM gene were identified in six cases (0.8%). Notably, one recurrent LPV, c.6115G > A:p.Glu2039Lys was identified in three cases, for which haplotype analysis confirmed as a novel putative founder mutation traced back to 13 generations on average. This founder mutation accounted for half of all identified mutant cases and 0.4% of total screened cases. This study further reveals a significant correlation between the presence of ATM mutation and family history of BC (p = 0.0127). These findings underscore an approximate 0.8% prevalence of ATM germline PVs/LPVs in Arab BC patients without BRCA1/2 PVs/LPVs and suggest a founder effect of specific recurrent ATM mutation. These insights can help in the design of a genetic testing strategy tailored to the local population in Saudi Arabia, thereby, enabling more accurate clinical management and risk prediction.
Identifiants
pubmed: 38017116
doi: 10.1038/s41598-023-48231-0
pii: 10.1038/s41598-023-48231-0
pmc: PMC10684510
doi:
Substances chimiques
BRCA1 protein, human
0
BRCA1 Protein
0
BRCA2 protein, human
0
BRCA2 Protein
0
ATM protein, human
EC 2.7.11.1
Ataxia Telangiectasia Mutated Proteins
EC 2.7.11.1
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
20924Informations de copyright
© 2023. The Author(s).
Références
Breast Cancer Res Treat. 2017 Feb;161(3):597-604
pubmed: 27913932
Mol Phylogenet Evol. 2007 Oct;45(1):211-26
pubmed: 17467298
FEBS J. 2015 Sep;282(17):3424-37
pubmed: 26094658
Int J Cancer. 2016 Sep 1;139(5):1091-7
pubmed: 27082205
Cancer Res. 2001 Oct 15;61(20):7608-15
pubmed: 11606401
Nucleic Acids Res. 2010 Sep;38(16):e164
pubmed: 20601685
Onco Targets Ther. 2021 May 19;14:3309-3318
pubmed: 34040395
Am J Hum Genet. 2000 Feb;66(2):494-500
pubmed: 10677309
Bioinformatics. 2002 Jun;18(6):894-5
pubmed: 12075030
JCO Glob Oncol. 2022 Mar;8:e2100415
pubmed: 35259001
Hum Mutat. 2019 Jun;40(6):729-733
pubmed: 30825404
Eur J Breast Health. 2021 Jun 24;17(3):234-238
pubmed: 34263150
Sci Rep. 2023 May 11;13(1):7666
pubmed: 37169825
Saudi Med J. 2018 May;39(5):464-469
pubmed: 29738005
J Theor Biol. 2023 May 21;565:111467
pubmed: 36963627
Am J Hum Genet. 2005 Mar;76(3):449-62
pubmed: 15700229
Nat Genet. 2016 Sep;48(9):1071-6
pubmed: 27428751
Science. 2007 May 25;316(5828):1160-6
pubmed: 17525332
Int J Cancer. 2015 Mar 1;136(5):E359-86
pubmed: 25220842
Cancer. 2017 May 15;123(10):1721-1730
pubmed: 28085182
Nat Genet. 2006 Aug;38(8):873-5
pubmed: 16832357
Gynecol Oncol. 2015 Apr;137(1):86-92
pubmed: 25622547
J Natl Cancer Inst. 2005 Jun 1;97(11):813-22
pubmed: 15928302
Lancet Oncol. 2013 Sep;14(10):e417-24
pubmed: 23993386
Cancer. 2001 Aug 1;92(3):479-87
pubmed: 11505391
Bioinformatics. 2010 Mar 1;26(5):589-95
pubmed: 20080505
Hum Mol Genet. 1998;7(10):1555-63
pubmed: 9735376
Genome Res. 2010 Sep;20(9):1297-303
pubmed: 20644199
J Natl Compr Canc Netw. 2017 Jan;15(1):9-20
pubmed: 28040716
N Engl J Med. 2021 Feb 4;384(5):428-439
pubmed: 33471991
Clin Genet. 2000 Aug;58(2):106-10
pubmed: 11005142
Mod Pathol. 2005 Jul;18(7):891-7
pubmed: 15803183
Breast Cancer Res Treat. 2019 Apr;174(3):639-647
pubmed: 30607632
J Med Genet. 2016 Jun;53(6):366-76
pubmed: 26787654
Genet Med. 2015 May;17(5):405-24
pubmed: 25741868
N Engl J Med. 2015 Jun 4;372(23):2243-57
pubmed: 26014596
CA Cancer J Clin. 2022 Nov;72(6):524-541
pubmed: 36190501
Nature. 1995 Dec 21-28;378(6559):789-92
pubmed: 8524414
N Engl J Med. 2021 Feb 4;384(5):440-451
pubmed: 33471974
PLoS One. 2012;7(1):e30806
pubmed: 22295111
Hum Genet. 2017 Nov;136(11-12):1431-1444
pubmed: 28975465
Cancer Res. 2003 Jun 15;63(12):3325-33
pubmed: 12810666
Oncol Rep. 2008 Jun;19(6):1505-10
pubmed: 18497957
Science. 2010 Oct 22;330(6003):521-5
pubmed: 20966256
J Clin Endocrinol Metab. 2008 Feb;93(2):611-8
pubmed: 18000091
Arch Public Health. 2022 Jul 11;80(1):168
pubmed: 35818086
Science. 1994 Oct 7;266(5182):66-71
pubmed: 7545954
JAMA Oncol. 2017 Sep 01;3(9):1190-1196
pubmed: 28418444