دورية أكاديمية
أعرض في EDS

Inherited Mutations in DNA Damage Repair Genes in Italian Men with Metastatic Prostate Cancer: Results from the Meet-URO 10 Study.

التفاصيل البيبلوغرافية
العنوان: Inherited Mutations in DNA Damage Repair Genes in Italian Men with Metastatic Prostate Cancer: Results from the Meet-URO 10 Study.
المؤلفون: Casadei C; IRCCS Istituto Romagnolo per lo Studio dei Tumori (IRST) 'Dino Amadori', Meldola, Italy., Scarpi E; IRCCS Istituto Romagnolo per lo Studio dei Tumori (IRST) 'Dino Amadori', Meldola, Italy., Conteduca V; Policlinico Riuniti, University of Foggia, Foggia, Italy., Gurioli G; IRCCS Istituto Romagnolo per lo Studio dei Tumori (IRST) 'Dino Amadori', Meldola, Italy., Cursano MC; IRCCS Istituto Romagnolo per lo Studio dei Tumori (IRST) 'Dino Amadori', Meldola, Italy., Brighi N; IRCCS Istituto Romagnolo per lo Studio dei Tumori (IRST) 'Dino Amadori', Meldola, Italy., Lolli C; IRCCS Istituto Romagnolo per lo Studio dei Tumori (IRST) 'Dino Amadori', Meldola, Italy., Schepisi G; IRCCS Istituto Romagnolo per lo Studio dei Tumori (IRST) 'Dino Amadori', Meldola, Italy., Basso U; Istituto Oncologico Veneto IRCCS, Padova, Italy., Fornarini G; San Martino Hospital, Genova, Italy., Bleve S; IRCCS Istituto Romagnolo per lo Studio dei Tumori (IRST) 'Dino Amadori', Meldola, Italy., Farolfi A; IRCCS Istituto Romagnolo per lo Studio dei Tumori (IRST) 'Dino Amadori', Meldola, Italy., Altavilla A; IRCCS Istituto Romagnolo per lo Studio dei Tumori (IRST) 'Dino Amadori', Meldola, Italy., Burgio SL; IRCCS Istituto Romagnolo per lo Studio dei Tumori (IRST) 'Dino Amadori', Meldola, Italy., Giunta EF; IRCCS Istituto Romagnolo per lo Studio dei Tumori (IRST) 'Dino Amadori', Meldola, Italy., Gianni C; IRCCS Istituto Romagnolo per lo Studio dei Tumori (IRST) 'Dino Amadori', Meldola, Italy., Filograna A; IRCCS Istituto Romagnolo per lo Studio dei Tumori (IRST) 'Dino Amadori', Meldola, Italy., Ulivi P; IRCCS Istituto Romagnolo per lo Studio dei Tumori (IRST) 'Dino Amadori', Meldola, Italy., Olmos D; Hospital Universitario 12 de Octubre, Madrid, Spain., Castro E; Instituto de Investigación Biomédica de Málaga (IBIMA), Málaga, Spain., De Giorgi U; IRCCS Istituto Romagnolo per lo Studio dei Tumori (IRST) 'Dino Amadori', Meldola, Italy.
المصدر: European urology open science [Eur Urol Open Sci] 2024 Feb 07; Vol. 61, pp. 44-51. Date of Electronic Publication: 2024 Feb 07 (Print Publication: 2024).
نوع المنشور: Journal Article
اللغة: English
بيانات الدورية: Publisher: Elsevier B.V Country of Publication: Netherlands NLM ID: 101771568 Publication Model: eCollection Cited Medium: Internet ISSN: 2666-1683 (Electronic) Linking ISSN: 26661683 NLM ISO Abbreviation: Eur Urol Open Sci Subsets: PubMed not MEDLINE
أسماء مطبوعة: Original Publication: [Amsterdam] : Elsevier B.V., [2020]-
مستخلص: Background: The prevalence of pathogenic germline mutations in DNA damage repair (gDDR) genes in the Italian population is unknown.
Objective: In this prospective multicenter cohort study, we evaluated the prevalence of gDDR alterations in the Italian population affected by metastatic prostate cancer (mPCa) and analyzed the impact on response to therapy, survival, and time to castration resistance.
Design Setting and Participants: In an observational prospective trial, 300 consecutive Italian mPCa patients, enrolled in the Meet-Uro-10 trial from three academic Italian centers, were recruited between 2017 and 2019 and were screened for gDDR mutations in 107 genes.
Outcome Measurements and Statistical Analysis: The primary endpoint was to assess the prevalence of gDDR mutations in the Italian population of patients with mPCa. The secondary endpoints included the association of gDDR subgroups with metastatic onset, Gleason score, and time to castration resistance.
Results and Limitations: We identified 297 valuable patients. Forty-six patients had a pathogenic/likely pathogenic variant (15.5%, 95% confidence interval: 11.4-19.6): the more frequent was gBRCA2 found in nine cases (3%), followed by gATM in five cases (1.7%). In patients without mutations, longer median overall survival was observed with the sequence docetaxel-androgen receptor signaling inhibitor (ARSI) than with the sequence ARSI-docetaxel (87.9 vs 42 mo, p  = 0.0001). In a univariate analysis, the median time to castration resistance in gDDR mutated patients was 19.8 mo, versus 23.7 mo in no mutated patients ( p  = 0.024). There were no associations of gDDR subgroups with metastatic onset and Gleason score ≥8. In our cohort, variants of unknown significance in gDDR genes were found in 80 patients and might have a prognostic relevance.
Conclusions: The study reported the prevalence of gDDR in the Italian population. The presence of gBRCA2 mutations correlates with a shorter time to the onset of castration resistance disease.
Patient Summary: The prevalence of gBRCA2 in the Italian population is 3%, which is similar to that in the Spanish population, identifying similarities between people of the Western Mediterranean area.
(© 2024 The Authors.)
References: Cell. 2015 May 21;161(5):1215-1228. (PMID: 26000489)
Eur Urol. 2017 Jul;72(1):34-42. (PMID: 28259476)
Am J Epidemiol. 2006 Mar 15;163(6):493-501. (PMID: 16443796)
Nat Commun. 2019 Nov 20;10(1):5251. (PMID: 31748536)
Nature. 2020 Feb;578(7793):82-93. (PMID: 32025007)
Proc Natl Acad Sci U S A. 2019 Jun 4;116(23):11428-11436. (PMID: 31061129)
JAMA Oncol. 2021 Jan 01;7(1):107-110. (PMID: 33151258)
Endocr Relat Cancer. 2014 May 08;21(3):487-93. (PMID: 24741024)
Lancet Oncol. 2020 Jan;21(1):162-174. (PMID: 31806540)
Eur Urol. 2021 Apr;79(4):519-529. (PMID: 33494937)
JAMA Oncol. 2023 Nov 1;9(11):1514-1524. (PMID: 37733366)
J Clin Oncol. 2013 May 10;31(14):1748-57. (PMID: 23569316)
Eur Urol. 2018 Aug;74(2):218-225. (PMID: 29439820)
Br J Cancer. 2021 Feb;124(3):552-563. (PMID: 33106584)
JAMA Oncol. 2019 Apr 01;5(4):523-528. (PMID: 30730552)
J Natl Compr Canc Netw. 2021 Oct 15;20(1):54-62. (PMID: 34653963)
Hum Mutat. 2008 Nov;29(11):1282-91. (PMID: 18951446)
J Clin Oncol. 2019 Feb 20;37(6):490-503. (PMID: 30625039)
Int J Oncol. 2019 Sep;55(3):597-616. (PMID: 31322208)
Dis Markers. 2016;2016:4358292. (PMID: 27594734)
Genes (Basel). 2021 May 20;12(5):. (PMID: 34065235)
BMC Cancer. 2020 Jun 3;20(1):507. (PMID: 32493233)
N Engl J Med. 2022 Mar 24;386(12):1132-1142. (PMID: 35179323)
Lancet. 2023 Jul 22;402(10398):291-303. (PMID: 37285865)
Oncotarget. 2020 Jan 28;11(4):440-442. (PMID: 32064047)
J Clin Oncol. 2008 Mar 1;26(7):1148-59. (PMID: 18309951)
Lancet Oncol. 2023 Oct;24(10):1094-1108. (PMID: 37714168)
Eur J Nucl Med Mol Imaging. 2018 Nov;45(12):2035-2044. (PMID: 29922948)
N Engl J Med. 2020 May 28;382(22):2091-2102. (PMID: 32343890)
Nat Genet. 2019 May;51(5):912-919. (PMID: 30988514)
Genome Biol. 2016 Feb 22;17:31. (PMID: 26899170)
Cancer Immunol Immunother. 2022 Apr;71(4):943-951. (PMID: 34533610)
N Engl J Med. 2016 Aug 4;375(5):443-53. (PMID: 27433846)
Cell Res. 2008 Jan;18(1):99-113. (PMID: 18166982)
فهرسة مساهمة: Keywords: DNA damage repair gene mutations; Germline BRCA2 mutations; Metastatic prostate cancer; Precision medicine
تواريخ الأحداث: Date Created: 20240222 Latest Revision: 20240224
رمز التحديث: 20240224
مُعرف محوري في PubMed: PMC10879937
DOI: 10.1016/j.euros.2024.01.015
PMID: 38384439
قاعدة البيانات: MEDLINE
الوصف
تدمد:2666-1683
DOI:10.1016/j.euros.2024.01.015