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. 2020 Jul 24;11:3726. doi: 10.1038/s41467-020-17127-2

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© The Author(s) 2020

Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.

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Fig. 1 — a Drug-response curves of survival after PARPi (olaparib, left) and carboplatin (right) treatment in HR-deficient parental cells (PEO1, BRCA2^MUT; JHOS4, BRCA1^MUT), acquired PARPi-resistant cells (PEO1-PR; JHOS4-PR), and carboplatin-resistant cells (PEO1-CR, and OVCAR3 with CCNE1^AMP) at 5 days. Nonlinear regression curve was generated using MTT data (dose–response inhibition). IC₅₀ was calculated by Graph Pad Prism. The fitted midpoints (lC50) of the two curves statistically compared by Extra sum-of squares F test (one-way). Mean ± SD shown (n = 3 independent biological replicates per treatment; experiment repeated at least thrice). PEO1 vs PEO1-PR, P < 0.0001; JHOS4 vs JHOS4-PR, P < 0.0001; PEO1 vs PEO1-CR, P < 0.0001; PEO1 vs OVCAR3, P < 0.0001. b Heatmap of genes and structural alterations present in samples from parental BRCA^MUT (JHOS4 and PEO1), acquired PARPi-resistant (PEO1-PR, PR1, PR2; JHOS4-PR, PR1, and PR2), and acquired carboplatin-resistant cell line (PEO1-CR, CR1, and CR2). Each column represents a separate alteration by either sequence or structural change, while each row represents a cell line. c Circos plots depict copy-number alterations as well as intra- and inter-chromosomal rearrangements. Focal amplifications in yellow, and focal deletions in green. Inter- and intra-chromosomal rearrangements in blue. d Parental (BRCA^MUT PEO1, JHOS4, and UWB; CCNE1 copy normal, OVKATE), acquired PARPi-resistant (PEO1-PR and JHOS4-PR), de novo PARPi-resistant (PEO4, Kuramochi, and UWB/BRCA1+/−), and platinum-resistant cells (PEO1-CR; CCNE1^Amp OVCAR3, FUOV1, and COV318) were treated with PARPi 1 μM and lysates were collected at 0, 2, 6 h. Cells were selected in PARPi or carboplatin and tested after a 10-day drug washout (except CCNE1^AMP cells). Western blot for the indicated phospho and total proteins was performed. Representative data shown are one of three independent biological repeat experiments. Source data are provided as a source data file.