The study analyzed 30 plasma and tumor samples from patients with high-grade serous ovarian cancer (HGSC) to detect BRCA1/2 mutations and reversions. BRCA1/2 mutations were found in all tumor samples, while reversions were found in 4 recurrent HGSC tumor samples. Reversions were also detected in the cell-free DNA from plasma samples of those 4 patients. The presence of reversions in tumor samples predicted chemotherapy resistance and relapse, showing the potential for liquid biopsies to noninvasively predict treatment outcomes in HGSC patients.

1. Elizabeth L. et al. (2017) DOI: 10.1200/JCO.2016.70.4627
30 plasma (blood) and tumor samples obtained
Group I: Patients with history of malignancy before
diagnosis of HGSC
Group II: Patients with recurrent HGSC
- performed using primers flanking BRCA1/2 mutations
- primer design not based on prior knowledge of reversion
sequences
- reversions analyzed in both tumor and plasma samples
- results subsequently matched to understand significance
of cf-DNA liquid biopsy in identifying BRCA1/2 mutations
and reversions
- BRCA1/2 mutations found in all analyzed tumor samples
- reversions found in only 4 tumor samples from group II
Targeted Amplicon Sequencing
Chemotherapy with platins and poly-ADP ribose
polymerase inhibitor-based drugs is ineffective in patients
with BRCA1/2 reversion mutations
Liquid Biopsy
Targeted Amplicon
Sequencing
Patients with BRCA1/2 reversions
in tumor samples
Positive predictive value = 1
Negative predictive value = 0.9
PatientswithBRCA1/2
reversionsinplasmasamples
Positive
Positive
Negative
Negative
True positive False positive
True negativeFalse negative
4 0
242
Patients with BCRA1/2 reversions
Emergence of drug
resistance and relapse
Chemotherapy
Reversion of BRCA1/2 Germline Mutations Detected in Circulating Tumor DNA From Patients With High-Grade Serous Ovarian Cancer
Predicting Therapeutic Outcome in High-Grade Serous
Ovarian Cancer by Circulating DNA Analysis
Chemotherapy response in patients with HGSC can be predicted using a noninvasive liquid biopsy
- mutations favor response to chemtherapy
- reversions could result in chemoresistance
Cell-Free DNA (cf-DNA)
- freely circulating molecules in blood
- contain DNA of tumor origin
Liquid Biopsy
- can analyze BRCA1/2 mutations in cf-DNA samples
- can predict treatment outcome if successful
BRCA1/2 mutations
& reversions
30 patients with HGSC with BRCA1/2 mutations
HGSC = High-Grade Serous Ovarian Cancer
Background
Methodology
Results
Outcome
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