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

Authors :
Konstantin Weber-Lassalle
Corinna Ernst
Alexander Reuss
Kathrin Möllenhoff
Klaus Baumann
Christian Jackisch
Jan Hauke
Dimo Dietrich
Julika Borde
Tjoung-Won Park-Simon
Lars Hanker
Katharina Prieske
Sandra Schmidt
Nana Weber-Lassalle
Esther Pohl-Rescigno
Stefan Kommoss
Frederik Marmé
Florian Heitz
Julia C Stingl
Rita K Schmutzler
Philipp Harter
Eric Hahnen
Source :
JNCI: Journal of the National Cancer Institute. 114:565-570
Publication Year :
2021
Publisher :
Oxford University Press (OUP), 2021.

Abstract

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 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.

Subjects

Subjects :
Cancer Research
Oncology

Details

ISSN :
14602105 and 00278874
Volume :
114
Database :
OpenAIRE
Journal :
JNCI: Journal of the National Cancer Institute
Accession number :
edsair.doi...........f56610c3fe59dfd71c38708a0e523714