Fig. 2

Patient with BRCA2-deleted, COSMIC signature 3 uLMS responded to PARPi. A Timeline of uLMS122 patient history (TAH = Total abdominal hysterectomy, BSO = Bilateral Salpingo-oophorectomy, NED = no evidence of disease). Repeated from Fig. 1B for ease of reference. B Structural variants plot generated from WGS data of first patient sample showing intra-chromosomal rearrangements. C Copy number profile generated from the first patient sample where total copy number is shown in black and minor copy number in red. Red at 0 indicates loss of heterozygosity. D Computerised tomography images of patient lungs at the point of recruitment to the SFRCP (i) and after 3 months of receiving olaparib (ii). E computerised tomography images of the patient lungs indicating a small recurrence (mediastinal nodule, blue cross) following the initial PARPi therapy (i) and following cisplatin plus PARPi. F Schematic of tumour samples analysed by WGS, with second sample showing additional PRKDC mutations (del = deletion, fs = frameshift). G Schematic depicting repair of DNA double stranded breaks (DSB) by either homologous recombination (HR) or Non-homologous end-joining (NHEJ), in which DNA PKcs plays a pivotal role