Clonal Hematopoiesis-Associated Gene Mutations in a Clinical Cohort of 448 Patients With Ovarian Cancer.

Carcinoma, Ovarian Epithelial Clonal Hematopoiesis Humans Mutation Ovarian Neoplasms / drug therapy Retrospective Studies

Journal

Journal of the National Cancer Institute
ISSN: 1460-2105
Titre abrégé: J Natl Cancer Inst
Pays: United States
ID NLM: 7503089

Informations de publication

Date de publication:
11 04 2022
Historique:
received: 16 04 2021
revised: 01 09 2021
accepted: 20 12 2021
pubmed: 29 12 2021
medline: 14 4 2022
entrez: 28 12 2021
Statut: ppublish

Résumé

Cancer patients are at risk of secondary therapy-related myeloid neoplasms (t-MNs). Acquired blood-specific mutations in clonal hematopoiesis (CH)-associated genes are t-MN risk factors, and their occurrence associated with cancer therapy and age. Patients with ovarian cancer (OC) showed a particularly high prevalence of CH-associated gene mutations, which may additionally be explained by the high proportion of a hereditary disease cause in this cancer entity. We performed a retrospective analysis of 448 OC patients enrolled in the AGO-TR1 study; 249 were enrolled at primary diagnosis and 199 at platinum-sensitive recurrence. Analyses included the most frequently altered CH-associated genes (ASXL1, DNMT3A, GNAS, JAK2, PPM1D, SF3B1, SH2B3, SRSF2, TET2, TP53). Results were analyzed according to the BRCA1/2 germline (gBRCA1/2) mutation status. All statistical tests were 2-sided. Advanced age at blood draw and a high number of prior platinum-based chemotherapy lines were risk factors to acquire CH-associated gene mutations, with gene-specific effects observed. Binomial logistic regression suggested increased probabilities for gBRCA1/2 mutation carriers to acquire CH-associated PPM1D and TP53 gene mutations (PPM1D: odds ratio = 4.30, 95% confidence interval = 1.48 to 12.46, P = .007; TP53: odds ratio = 6.20, 95% confidence interval = 0.98 to 53.9, P = .06). This observation was due to a statistically significantly increased number of platinum-based chemotherapy lines in gBRCA1/2 mutation carriers vs noncarriers (PPM1D: mean [SD] = 2.04 [1.27] vs 1.04 [0.99], P < .001; TP53: mean [SD] = 2.83 [1.33] vs 1.07 [1.01], P < .001). No interaction between platinum-based chemotherapy and gBRCA1/2 mutation status with the occurrence of CH-associated gene mutations was observed. A positive gBRCA1/2 mutation status is not a risk factor to acquire CH-associated gene mutations. OC patients may benefit from monitoring CH-associated gene mutations, especially following carboplatin exposure. Future clinical studies are required to assess whether treatment regimen should be adapted according to individual t-MN risks.

Sections du résumé

BACKGROUND
Cancer patients are at risk of secondary therapy-related myeloid neoplasms (t-MNs). Acquired blood-specific mutations in clonal hematopoiesis (CH)-associated genes are t-MN risk factors, and their occurrence associated with cancer therapy and age. Patients with ovarian cancer (OC) showed a particularly high prevalence of CH-associated gene mutations, which may additionally be explained by the high proportion of a hereditary disease cause in this cancer entity.
METHODS
We performed a retrospective analysis of 448 OC patients enrolled in the AGO-TR1 study; 249 were enrolled at primary diagnosis and 199 at platinum-sensitive recurrence. Analyses included the most frequently altered CH-associated genes (ASXL1, DNMT3A, GNAS, JAK2, PPM1D, SF3B1, SH2B3, SRSF2, TET2, TP53). Results were analyzed according to the BRCA1/2 germline (gBRCA1/2) mutation status. All statistical tests were 2-sided.
RESULTS
Advanced age at blood draw and a high number of prior platinum-based chemotherapy lines were risk factors to acquire CH-associated gene mutations, with gene-specific effects observed. Binomial logistic regression suggested increased probabilities for gBRCA1/2 mutation carriers to acquire CH-associated PPM1D and TP53 gene mutations (PPM1D: odds ratio = 4.30, 95% confidence interval = 1.48 to 12.46, P = .007; TP53: odds ratio = 6.20, 95% confidence interval = 0.98 to 53.9, P = .06). This observation was due to a statistically significantly increased number of platinum-based chemotherapy lines in gBRCA1/2 mutation carriers vs noncarriers (PPM1D: mean [SD] = 2.04 [1.27] vs 1.04 [0.99], P < .001; TP53: mean [SD] = 2.83 [1.33] vs 1.07 [1.01], P < .001). No interaction between platinum-based chemotherapy and gBRCA1/2 mutation status with the occurrence of CH-associated gene mutations was observed.
CONCLUSIONS
A positive gBRCA1/2 mutation status is not a risk factor to acquire CH-associated gene mutations. OC patients may benefit from monitoring CH-associated gene mutations, especially following carboplatin exposure. Future clinical studies are required to assess whether treatment regimen should be adapted according to individual t-MN risks.

Identifiants

DOI: 10.1093/jnci/djab231 PMID: 34963005 PMC: PMC9002281
pubmed: 34963005
pii: 6486427
doi: 10.1093/jnci/djab231
pmc: PMC9002281
doi:

Types de publication

Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

565-570

Commentaires et corrections

Type : CommentIn

Informations de copyright

© The Author(s) 2021. Published by Oxford University Press. All rights reserved. For permissions, please email: journals.permissions@oup.com.

Références

N Engl J Med. 2014 Dec 25;371(26):2477-87
pubmed: 25426838
Breast Care (Basel). 2017 Mar;12(1):15-19
pubmed: 28611536
Nat Genet. 2020 Nov;52(11):1219-1226
pubmed: 33106634
Clin Cancer Res. 2014 Feb 1;20(3):764-75
pubmed: 24240112
Lancet Oncol. 2021 May;22(5):620-631
pubmed: 33743851
Gynecol Oncol. 2020 Nov;159(2):442-448
pubmed: 32981695
Cell Stem Cell. 2018 Nov 1;23(5):700-713.e6
pubmed: 30388424
Fly (Austin). 2012 Apr-Jun;6(2):80-92
pubmed: 22728672
J Med Genet. 2019 Sep;56(9):574-580
pubmed: 30979843
Bioinformatics. 2009 Aug 15;25(16):2078-9
pubmed: 19505943
Bioinformatics. 2009 Jul 15;25(14):1754-60
pubmed: 19451168
Sci Rep. 2017 May 8;7(1):1567
pubmed: 28484262
JAMA. 2012 Jan 25;307(4):382-90
pubmed: 22274685
JCO Precis Oncol. 2017 Jul;2017:
pubmed: 28890946
Nat Med. 2014 Dec;20(12):1472-8
pubmed: 25326804
Blood. 2018 Sep 13;132(11):1095-1105
pubmed: 29954749
PLoS One. 2017 Oct 20;12(10):e0186043
pubmed: 29053726
Eur J Cancer. 2016 Jul;61:137-45
pubmed: 27209246

Auteurs

Konstantin Weber-Lassalle (K)

Center for Familial Breast and Ovarian Cancer, Center for Integrated Oncology (CIO), University of Cologne, Faculty of Medicine and University Hospital Cologne, Cologne, Germany.

Corinna Ernst (C)

Center for Familial Breast and Ovarian Cancer, Center for Integrated Oncology (CIO), University of Cologne, Faculty of Medicine and University Hospital Cologne, Cologne, Germany.
ORCID: 0000-0001-7756-8815

Alexander Reuss (A)

Coordinating Center for Clinical Trials, Philipps-University Marburg, Marburg, Germany.

Kathrin Möllenhoff (K)

Institute of Medical Statistics and Computational Biology, Faculty of Medicine, University of Cologne, Cologne, Germany.

Klaus Baumann (K)

Department of Gynecology, Medical Center Ludwigshafen, Ludwigshafen, Germany.
ORCID: 0000-0001-5333-9823

Christian Jackisch (C)

Department of Gynecology and Obstetrics, Sana Klinikum Offenbach, Offenbach, Germany.
ORCID: 0000-0001-8537-3743

Jan Hauke (J)

Center for Familial Breast and Ovarian Cancer, Center for Integrated Oncology (CIO), University of Cologne, Faculty of Medicine and University Hospital Cologne, Cologne, Germany.
ORCID: 0000-0001-8236-4075

Dimo Dietrich (D)

Department of Otorhinolaryngology, Head and Neck Surgery, University Medical Center Bonn (UKB), Bonn, Germany.
ORCID: 0000-0001-9794-7927

Julika Borde (J)

Center for Familial Breast and Ovarian Cancer, Center for Integrated Oncology (CIO), University of Cologne, Faculty of Medicine and University Hospital Cologne, Cologne, Germany.
ORCID: 0000-0003-2448-7872

Tjoung-Won Park-Simon (TW)

Department of Gynecology & Gynecologic Oncology, Medizinische Hochschule Hannover, Hannover, Germany.
ORCID: 0000-0002-2863-3040

Lars Hanker (L)

Department of Gynecology and Obstetrics, University of Schleswig-Holstein, Lübeck, Germany.
ORCID: 0000-0001-6697-018X

Katharina Prieske (K)

Department of Gynecology and Gynecologic Oncology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
ORCID: 0000-0002-4245-6503

Sandra Schmidt (S)

Center for Familial Breast and Ovarian Cancer, Center for Integrated Oncology (CIO), University of Cologne, Faculty of Medicine and University Hospital Cologne, Cologne, Germany.

Nana Weber-Lassalle (N)

Center for Familial Breast and Ovarian Cancer, Center for Integrated Oncology (CIO), University of Cologne, Faculty of Medicine and University Hospital Cologne, Cologne, Germany.

Esther Pohl-Rescigno (E)

Center for Familial Breast and Ovarian Cancer, Center for Integrated Oncology (CIO), University of Cologne, Faculty of Medicine and University Hospital Cologne, Cologne, Germany.

Stefan Kommoss (S)

Department Gynecology & Gynecologic Oncology, University of Tübingen, Tübingen, Germany.
ORCID: 0000-0003-0534-1501

Frederik Marmé (F)

Center for Tumor Disease, Department of Gynecology, University of Heidelberg, Heidelberg, Germany.

Florian Heitz (F)

Department of Gynecology & Gynecologic Oncology, Kliniken Essen-Mitte (KEM) Evang, Huyssens-Stiftung/Knappschaft GmbH, Essen, Germany.
Department for Gynecology, Charité - Universitätsmedizin Berlin, Freie Universität Berlin, Humboldt-Universität zu Berlin, Berlin, Germany.
Berlin Institute of Health, Berlin, Germany.
ORCID: 0000-0002-2412-0352

Julia C Stingl (JC)

Institute of Clinical Pharmacology, University Hospital of Rheinisch-Westfälische Technische Hochschule Aachen, Aachen, Germany.
ORCID: 0000-0002-1566-8156

Rita K Schmutzler (RK)

Center for Familial Breast and Ovarian Cancer, Center for Integrated Oncology (CIO), University of Cologne, Faculty of Medicine and University Hospital Cologne, Cologne, Germany.

Philipp Harter (P)

Department of Gynecology & Gynecologic Oncology, Kliniken Essen-Mitte (KEM) Evang, Huyssens-Stiftung/Knappschaft GmbH, Essen, Germany.
ORCID: 0000-0002-9663-5005

Eric Hahnen (E)

Center for Familial Breast and Ovarian Cancer, Center for Integrated Oncology (CIO), University of Cologne, Faculty of Medicine and University Hospital Cologne, Cologne, Germany.

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Classifications MeSH

questionsmedicales.fr › Maladies endocriniennes › Troubles gonadiques › Maladies ovariennes › Tumeurs de l'ovaire › Carcinome épithélial de l'ovaire › Clonal Hematopoiesis-Associated Gene Mutations...
questionsmedicales.fr › Phénomènes physiologiques respiratoires et circulatoires › Phénomènes physiogiques du sang › Hématopoïèse › Hématopoïèse clonale › Clonal Hematopoiesis-Associated Gene Mutations...
questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Primates › Haplorhini › Catarrhini › Hominidae › Humains › Clonal Hematopoiesis-Associated Gene Mutations...
questionsmedicales.fr › Phénomènes génétiques › Variation génétique › Mutation › Clonal Hematopoiesis-Associated Gene Mutations...
questionsmedicales.fr › Maladies endocriniennes › Troubles gonadiques › Maladies ovariennes › Tumeurs de l'ovaire › Clonal Hematopoiesis-Associated Gene Mutations...
questionsmedicales.fr › Environnement et santé publique › Santé publique › Méthodes épidémiologiques › Caractéristiques des études épidémiologiques › Études épidémiologiques › Études de cohortes › Études rétrospectives › Clonal Hematopoiesis-Associated Gene Mutations...