Weber-Lassalle, Konstantin, Ernst, Corinna, Reuss, Alexander, Mollenhoff, Kathrin ORCID: 0000-0001-7861-3892, Baumann, Klaus, Jackisch, Christian, Hauke, Jan, Dietrich, Dimo, Borde, Julika, Park-Simon, Tjoung-Won, Hanker, Lars, Prieske, Katharina, Schmidt, Sandra, Weber-Lassalle, Nana, Pohl-Rescigno, Esther, Kommoss, Stefan, Marme, Frederik, Heitz, Florian, Stingl, Julia C., Schmutzler, Rita K., Harter, Philipp and Hahnen, Eric . Clonal Hematopoiesis-Associated Gene Mutations in a Clinical Cohort of 448 Patients With Ovarian Cancer. JNCI-J. Natl. Cancer Inst.. CARY: OXFORD UNIV PRESS INC. ISSN 1460-2105

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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 < .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.

Item Type: Journal Article
Creators:
CreatorsEmailORCIDORCID Put Code
Weber-Lassalle, KonstantinUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Ernst, CorinnaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Reuss, AlexanderUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Mollenhoff, KathrinUNSPECIFIEDorcid.org/0000-0001-7861-3892UNSPECIFIED
Baumann, KlausUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Jackisch, ChristianUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Hauke, JanUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Dietrich, DimoUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Borde, JulikaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Park-Simon, Tjoung-WonUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Hanker, LarsUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Prieske, KatharinaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Schmidt, SandraUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Weber-Lassalle, NanaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Pohl-Rescigno, EstherUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Kommoss, StefanUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Marme, FrederikUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Heitz, FlorianUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Stingl, Julia C.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Schmutzler, Rita K.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Harter, PhilippUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Hahnen, EricUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
URN: urn:nbn:de:hbz:38-603611
DOI: 10.1093/jnci/djab231
Journal or Publication Title: JNCI-J. Natl. Cancer Inst.
Publisher: OXFORD UNIV PRESS INC
Place of Publication: CARY
ISSN: 1460-2105
Language: English
Faculty: Unspecified
Divisions: Unspecified
Subjects: no entry
Uncontrolled Keywords:
KeywordsLanguage
GERMLINE; SURVIVALMultiple languages
OncologyMultiple languages
URI: http://kups.ub.uni-koeln.de/id/eprint/60361

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