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Figure S4 from Genome-wide Copy-number Alterations in Circulating Tumor DNA as a Novel Biomarker for Patients with High-grade Serous Ovarian Cancer

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posted on 2023-03-31, 23:07 authored by Lara Paracchini, Luca Beltrame, Tommaso Grassi, Alessia Inglesi, Robert Fruscio, Fabio Landoni, Davide Ippolito, Martina Delle Marchette, Mariachiara Paderno, Marco Adorni, Marta Jaconi, Chiara Romualdi, Maurizio D'Incalci, Giulia Siravegna, Sergio Marchini

Dynamic changes of TF and CNI in patients receiving front line chemotherapy. Bar plots of average percentage distribution of TF (A, B) or CNI (C, D) values in plasma of HGS-EOC at T=0 and at different time points of the "treatment window" (A0 to A1, and N0 to N4). Data are separated according to the different protocols they received: panels A, and C depict patients receiving CT while panels B and D depict patients receiving NACT protocol. Within each box, the horizontal line represents the median distribution, the box margins the 25% and 75% percentiles, and the whiskers the 5% and 95% percentiles. Blue circles, Pt-ps patients. Red circles, Pt-r patients. Green circles, Pt-s patients. *, p< 0.05; ** p <0.01; *** p<0.001, according to the Mann-Whitney test.

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Italian Association for Cancer Research

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ARTICLE ABSTRACT

High-grade serous epithelial ovarian cancer (HGS-EOC) is defined by high levels of somatic copy-number alterations (SCNA) with marked spatial and temporal tumor heterogeneity. Biomarkers serving to monitor drug response and detect disease recurrence are lacking, a fact which reflects an unmet clinical need. A total of 185 plasma samples and 109 matched tumor biopsies were collected from 46 patients with HGS-EOC, and analyzed by shallow whole-genome sequencing (sWGS). The percentage of tumor fraction (TF) in the plasma was used to study the biological features of the disease at the time of diagnosis (T0) and correlated with patients' survival. Longitudinal analysis of TF was correlated with CA-125 levels and radiological images to monitor disease recurrence. Gain in the clonal regions, 3q26.2 and 8q24.3, was observed in the 87.8% and 78.05% of plasma samples, suggesting that plasma sWGS mirrors solid biopsies. At T0, multivariate analysis revealed that plasma TF levels were an independent prognostic marker of relapse (P < 0.022). After platinum (Pt)-based treatment, circulating tumor DNA (ctDNA) analysis showed a change in the heterogeneous pattern of genomic amplification, including an increased frequency of amplification, compared with before Pt-based treatment in the 19p31.11 and 19q13.42 regions. TF in serially collected ctDNA samples outperformed CA-125 in anticipating clinical and radiological progression by 240 days (range, 37–491). Our results support the notion that sWGS is an inexpensive and useful tool for the genomic analysis of ctDNA in patients with HGS-EOC to monitor disease evolution and to anticipate relapse better than serum CA-125, the routinely used clinical biomarker.See related commentary by Dhani, p. 2372

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