Circulating tumor DNA genomic profiling reveals the complicated olaparib-resistance mechanism in prostate cancer salvage therapy: A case report

Figure 1 Radiological and immunohistochemical results showing metastatic hormone-sensitive prostate cancer. A: Sagittal magnetic resonance imaging (MRI) showed multiple lumbar vertebrate metastases; B: Bone scanning displayed the high metabolic activity of bone lesions; C: Cross (left) and sagittal (right) sections of MRI scanning (T2WI) displayed invasion of the prostate malignant lesion into the bladder wall as well as the seminal vesicle; D: Hematoxylin-eosinstaining and immunohistochemistry results for androgen receptor, NKX3.1, and periodic Schiff Acid staining. Original magnification: 100 ×; scale bar: 100 μm. HE: Hematoxylin-eosin; AR: Androgen receptor; PSA: Periodic Schiff Acid.

Figure 2 Circulating tumor cells and dynamic change of serum total prostate-specific antigen level. A: Dynamic change of serum total prostate-specific antigen level during the overall treatment with various therapeutic approaches (androgen-deprivation therapy; docetaxel; abiraterone; clinical trial; the PARP inhibitor, olaparib); B: The epithelial-circulating tumor cell (E-CTC), mesenchymal-CTC (M-CTC) and epithelial mesenchymal transition-CTC (EMT-CTC) counts and change before (2017-06-13) and after (2018-06-19) abiraterone treatment. Expression of AR-V7 mRNA was detected in these CTCs; C: Representative graphs displaying the E-CTC, M-CTC and EMT-CTC. Red signal: Probe mixture for detection of mRNA of EpCAM, CK8, CK18, and CK19; Green signal: Probe mixture for detection of mRNA of vimentin and Twist. CTC: Circulating tumor cell.

Figure 3 Diagram of the predicted homologous recombination repair gene PALB2 protein sequence changes caused by the germline mutation (c. 751C>T) and the two somatic reverse mutations (c.751_752delCAinsTT and c.751_753delCAGinsTAC) on the same loci detected in ctDNA from the patient presenting with resistance of olaparib PAPR inhibitor in combination with abiraterone. HRR: Homologous recombination repair; PALB2: Partner and localizer of BRCA2; WT: Wild-type. Stop codon; nonsense mutation.