|Genomic Loss of Heterozygosity||Large-Scale State Transitions|
Caris reports HRD status based on BRCA1 or BRCA2 mutations and a Genomic Scar Score (GSS), comprised of genomic Loss of Heterozygosity (gLOH) plus Large-scale State Transitions (LST):
Either BRCA mutation detected or GSS = HIGH
BRCA mutation not detected and GSS = LOW
Reported for epithelial ovarian cancer cases (tissue profiling) at no additional cost or specimen requirements.*Not available in all locations.
Figure 1. Homologous Repair Deficiency (HRD) is the result of genetic alteration(s) in HR genes (eg, BRCA1, BRCA2 and others) or epigenetic factors. Dysfunctional HR genes result in genome-wide errors and tumorigenesis.
HRD-positive tumors rely heavily on the PARP pathway for tumor growth and are therefore highly sensitized to PARP-inhibitor therapy, which specifically disrupts an already diminished DNA repair system in these tumor cells.
|BIOMARKER||METHOD||ANALYTE||RESULT||THERAPY ASSOCIATIONS||BIOMARKER LEVEL*|
|HRD**||Seq||DNA-Tumor||Positive||BENEFIT||niraparib, olaparib, rucanparib||Level 2|
|BRCA1||Seq||DNA-Tumor||Pathogenic Variant Exon 10 | p.I650fs|
* Biomarker reporting classification: Level 1 – Companion Diagnostics (CDx); Level 2 – Strong evidence of clinical significance or is endorsed by standard clinical guidelines; Level 3 – Potential clinical significance. Bolded benefit therapies, if present, highlight the most clinically significant findings.
** HRD – homologous recombination deficiency status. A positive result is indicative of a pathogenic or likely pathogenic variant(s) in BRCA1 and/or BRCA2 or high Genomic Scar Score (LOH + LST) which consists of genomic Loss of Heterozygozity (gLOH) + Large-scale State Transitions (LST).
Place an order today for a comprehensive, personalized Caris profiling report.
1. Zhang H, Liu T, Zhang Z, et al. Integrated proteogenomic characterization of human high-grade serous ovarian cancer. Cell. 2016;166:755-765.
2. Sugino K, et al. Sci Rep. 2019;9:17808; Pennington KP, et al. Clin Cancer Res. 2014;20:764–775).
3. Ngoi NYL, Tan DSP. The role of homologous recombination deficiency testing in ovarian cancer and its clinical implications: do we need it? ESMO Open. 2021 Jun;6(3):100144.