Chemotherapy-induced mutations in genes of clonal hematopoiesis increase the risk of myeloid neoplasms

F Heitz; K Weber-Lassalle; C Ernst; K Möllenhoff; N de Gregorio; J Hauke; D Dietrich; J Borde; C Jackisch; T-W Park-Simon; LC Hanker; E Pohl-Rescigno; K Prieske; S Kommoss; F Marme; JC Stingl; S Rita; P Harter; E Hahnen

doi:10.1055/s-0042-1756857

Geburtshilfe und Frauenheilkunde, Inhaltsverzeichnis

Geburtshilfe Frauenheilkd 2022; 82(10): e88
DOI: 10.1055/s-0042-1756857

Abstracts | DGGG

Chemotherapy-induced mutations in genes of clonal hematopoiesis increase the risk of myeloid neoplasms

F Heitz

¹Kliniken Essen-Mitte, Gynäkologie und gynäkologische Onkologie, Essen, Deutschland

²Universitätsmedizin Berlin, Charité, Berlin, Klinik für Gynäkologie mit Zentrum für onkologische Chirurgie, Berlin, Deutschland

,

K Weber-Lassalle

³Medical Faculty, University Hospital Cologne, Cologne, Germany, Center for Hereditary Breast and Ovarian Cancer, Center for Integrated Oncology (CIO),, Köln, Deutschland

,

C Ernst

³Medical Faculty, University Hospital Cologne, Cologne, Germany, Center for Hereditary Breast and Ovarian Cancer, Center for Integrated Oncology (CIO),, Köln, Deutschland

,

K Möllenhoff

³Medical Faculty, University Hospital Cologne, Cologne, Germany, Center for Hereditary Breast and Ovarian Cancer, Center for Integrated Oncology (CIO),, Köln, Deutschland

,

N de Gregorio

⁴SLK-Kliniken Heilbronn GmbH, Klinikum am Gesundbrunnen, Frauenklinik, Heilbronn, Deutschland

,

J Hauke

³Medical Faculty, University Hospital Cologne, Cologne, Germany, Center for Hereditary Breast and Ovarian Cancer, Center for Integrated Oncology (CIO),, Köln, Deutschland

,

D Dietrich

³Medical Faculty, University Hospital Cologne, Cologne, Germany, Center for Hereditary Breast and Ovarian Cancer, Center for Integrated Oncology (CIO),, Köln, Deutschland

,

J Borde

³Medical Faculty, University Hospital Cologne, Cologne, Germany, Center for Hereditary Breast and Ovarian Cancer, Center for Integrated Oncology (CIO),, Köln, Deutschland

,

C Jackisch

⁵Sana Klinikum Offenbach, Frauenklinik, Offenbach, Deutschland

,

T-W Park-Simon

⁶Medizinische Hochschule Hannover, Frauenklinik – gynäkologische Onkologie, Hannover, Deutschland

,

LC Hanker

⁷Universitätsklinikum Schleswig-Holstein, Campus Lübeck, Klinik für Gynäkologie und Geburtshilfe, Lübeck, Deutschland

,

E Pohl-Rescigno

³Medical Faculty, University Hospital Cologne, Cologne, Germany, Center for Hereditary Breast and Ovarian Cancer, Center for Integrated Oncology (CIO),, Köln, Deutschland

,

K Prieske

⁸Universitätsklinikum Hamburg-Eppendorf, Klinik und Poliklinik für Gynäkologie, Hamburg, Deutschland

,

S Kommoss

⁹Universitätsklinikum Tübingen, Universitäts-Frauenklinik, Tübingen, Deutschland

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F Marme

¹⁰Universitätsklinikum Mannheim, Frauenklinik und Nationales Centrum f. Tumorerkrankungen, Universitäts-Frauenklinik, Gynäkologische Onkologie, Heidelberg, Mannheim, Deutschland

,

JC Stingl

³Medical Faculty, University Hospital Cologne, Cologne, Germany, Center for Hereditary Breast and Ovarian Cancer, Center for Integrated Oncology (CIO),, Köln, Deutschland

,

S Rita

³Medical Faculty, University Hospital Cologne, Cologne, Germany, Center for Hereditary Breast and Ovarian Cancer, Center for Integrated Oncology (CIO),, Köln, Deutschland

,

P Harter

¹Kliniken Essen-Mitte, Gynäkologie und gynäkologische Onkologie, Essen, Deutschland

,

E Hahnen

³Medical Faculty, University Hospital Cologne, Cologne, Germany, Center for Hereditary Breast and Ovarian Cancer, Center for Integrated Oncology (CIO),, Köln, Deutschland

› Institutsangaben

Abstract

Volltext

Objective To identify acquired blood-specific mutations in clonal hematopoiesis (CH) genes that influence the risk of secondary, therapy-associated myeloid neoplasia.

Materials and Methods Retrospective analysis of 448 patients with ovarian cancer (OC) enrolled in AGO-TR1-a retrospective cohort trial to evaluate the frequency of BRCA mutations in patients with OC. The following CH-associated genes were analyzed with NGS in germline DNA derived from blood cells. ASXL1, DNMT3A, GNAS, JAK2, PPM1D, SF3B1, SH2B3, SRSF2, TET2, TP53 were analysed with. Results were correlated with BRCA 1/2 status.

Results Older age and number of prior platinum-based chemotherapy lines were risk factors associated with increased frequency of acquired CH-associated mutations. Logistic regression analyses in gBRCA1/2 mutation carriers showed increased probabilities of acquired KH-associated mutations in PPM1D and TP53 (PPM1D: odds ratio (OR): 4.30, 95% CI:1.48 -12.46, P=.007; TP53: OR: 6.20, 95% CI:0.98- 53.9, P=.06). This observation was based on an increased number of platinum-based chemotherapy lines in gBRCA1/2 mutation carriers vs nonmutation carriers (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). There was no interaction between platinum-containing chemotherapy and gBRCA1/2 mutation status.

Summary gBRCA1/2 mutations are not risk factors for CH-associated gene mutations. Patients with OC may benefit from monitoring KH-associated genes after platinum-containing chemotherapy. Future studies should evaluate how far treatment regimens should be adjusted for the risk of developing therapy-associated myeloid neoplasms.