Investigator
Monash University
Performance Evaluation of a New HRD Assay (HRDsig) in Ovarian Carcinomas in Australia
ABSTRACTBackgroundHomologous recombination repair (HRR) is the preferred pathway for repairing double‐strand DNA breaks, using proteins like BRCA1 and BRCA2, among others, while the PARP‐mediated repair pathway is primarily used for single‐strand breaks. When a tumour becomes HRR‐deficient (HRD), then those tumour cells become reliant on PARP‐mediated repair. Poly ADP‐ribose polymerase inhibitors, olaparib and niraparib, have been approved in Australia for advanced (FIGO III‐IV), high‐grade serous or other high‐grade ovarian, fallopian tube or primary peritoneal carcinoma with homologous recombination deficiency (HRD).MethodsHRDsig (Roche Inc) is a new HRD biomarker that is part of the AVENIO Tumor Tissue CGP Kit V2. We have studied the performance of HRDsig against two NATA (National Association of Testing Authorities, Australia) accredited HRD assays in the cases of high‐grade ovarian carcinomas. We have evaluated the performance of HRDsig using a total 40 HRD results against the two accredited HRD assays, as well as against commercial controls and inter‐laboratory comparison samples.ResultsHRDsig has demonstrated a high concordance rate for HRD by comparing it with two different locally accredited HRD assays in cases of ovarian cancers.ConclusionThese findings provide real‐world evidence of the performance of a new HRD assay (HRDsig) in ovarian carcinomas.
Mutational landscape of ovarian carcinomas: An Australian study of 116 patients
Understanding genetic biomarkers in ovarian cancer allows for access to targeted clinical management. This retrospective mutational analysis of 116 Australian patients with ovarian cancer complements the development of current knowledge on ovarian cancer biomarkers. In the 116 samples, nearly 500 variants were identified including 19 variants of strong clinical significance, 212 variants of potential clinical significance and 268 variants of uncertain clinical significance (VUS) as per the Association for Molecular Pathology (AMP) guidelines. The most frequently altered gene was TP53 which was altered in 75 % of tumours. Other commonly altered genes included PIK3CA, PTEN, ARID1A, KRAS and BRCA1. Moreover, the biggest differences in between mutational profile was observed in between tumour subtypes, more specifically in between HGSOC and endometrioid tumour. Minimal differences in mutational landscape were identified between primary and metastatic lesions, with only PTEN being significantly more prevalent in primary lesions. PTEN and ARID1A pathogenic variants were more frequently reported in younger patient group. These genetic markers could be used to support clinical care, providing information for diagnosis, prognosis and therapeutic option for the patient.
