Homologous Recombination Repair (HRR) and Poly ADP-ribose Polymerase (PARP) Repair are two important mechanisms for DNA damage repair in double-strand and single-strand DNA, respectively. Gene mutations (e.g. BRCA1/2) in the HRR pathway can lead to Homologous Recombination Defect (HRD). PARP inhibitors can inhibit the repair of single-strand DNA damage in tumor cells, and if the repair mechanism of double-strand DNA is also affected by HRD, the tumor cells can be killed by “synthetic lethal” effect ^[1]. Studies have shown that HRD can exist in ~50% of the patients with high-grade serous ovarian cancer ^[2], so the evaluation of HRD status is of great significance in screening the sensitive population for PARP inhibitors.

Figure 1. The diagram of “synthetic lethal” effect of PARP inhibitors ^[1]      

 Figure 2. HRD is present in approximately 50% of the patients with high-grade serous ovarian cancer ^[2]

HRDetectCDx Panel is a NGS panel to detect and quantify HRD, independently developed by MEDx Translational Medicine. Based on the 41,000+ high-quality single nucleotide polymorphism sites (SNPs) screened from the ChinaMap database of 10,000 individuals, the Genomic Instability Score (Genomic Instability Score, GIS) can be calculated, by analyzing Loss of Heterozygosity (LOH), Telomere Allelic Imbalance (TAI), and Large-scale State Transitions (LST), etc., In order to meet the requirements from different clients, HRDetectCDx Panel has two versions: Mutation Version, Scoring Version.

Clinical Significance

√    HRD is present in approximately 50% of the patients with high-grade serous ovarian cancer

√    The HRD-positive patients is 2-3.5 times more than those with of BRCA1/2-positive only, which helps to find more patients benefiting from PARP inhibitors

√    Patients with high HRD values can be more sensitive to PARP inhibitors, compared to those with low HRD values

√   Patients with high HRD values can get more benefits from platinum-based chemotherapy regimens, compared to those with low HRD values

Advantages

√    Authoritative

①85 genes designed from authoritative guidelines, including the University of Washington consensus, NCCN guidelines, etc.

②41,000+ high-quality SNPs loci specifically for Chinese population, screened from the ChinaMap database of 10,000 individuals

√    Professional – Comprehensive GIS score, based on the optimized scoring algorithm specifically for Chinese population and the simultaneous analysis of three genomic instability indicators of LOH, TAI, and LST

√    Accurate - Ultra-high sequencing depth, ensuring the detection of  low-frequency sites

√    High-quality - Imported raw materials used to ensure the quality of testing

Applications

√    Patients with breast cancer (triple negative breast cancer, TNBC), ovarian cancer, prostate cancer, pancreatic cancer and peritoneal cancer, etc.

√    Patients with PARP Inhibitor therapy

√    Patients with platinum-based chemotherapy or other personalized therapy with homologous recombination inhibitors

Test procedure

Reporting Time

7 calendar days

Sample Requirements

References

［1］Amir Sonnenblick，et al. An update on PARP inhibitors—moving to the adjuvant setting，Nature Reviews Clinical Oncology volume 12, pages27‒41(2015).

［2］Jiang Xuan, et al. PARP inhibitors in ovarian cancer: Sensitivity prediction and resistance mechanisms, J Cell Mol Med. 2019:1‒11.