Original articles
Vol. 117: Issue 3 - June 2025
Homologous recombination deficiency testing in ovarian cancer: the diagnostic experience of a referral Italian institution
Abstract
Aims. Recently, precision medicine has drastically modified clinical paradigm for the clinical stratification of high-grade serous ovarian cancer (HGSOC) patients. International societies approved poly (ADP-ribose) polymerase (PARP) inhibitors (PARPIs) to treat platinumsensitive BRCA1/2 defective HGSOC patients. Beyond BRCA1/2, functional defects in homologous recombination repair (HRR) proteins laid the basis for genomic instability evaluation in HGSOC patients. Given that measurement of homologous recombination deficiency (HRD) is extremely complex molecular analysis is outsourced. Of note, this diagnostic algorithm is affected by inconclusive results and high rejection rates. Here, we review the molecular results of BRCA1/2 and HRD analysis from referral institution in predictive molecular pathology.
Methods. From May 2023 to Jan 2024 molecular records from 147 HGSOC patients simultaneously tested for BRCA1/2 and HRD measurement were inspected. A commercially available next-generation sequencing (NGS) panel (Amoy Diagnostics Co Ltd, Xiamen, Fujian, China) was adopted to internally perform molecular analysis on formalin-fixed paraffin- embedded (FFPE) samples. In a subset of patients clinical records were matched with molecular results.
Results. Overall, 2 out of 147 (1.3%) cases were morphologically classified as inadequate. Simultaneous BRCA1/2 - HRD analysis was successfully assessed in 112 out of 145 (77.2%) patents. Molecular analysis revealed 7 out of 112 (6.2%) and 2 out of 112 (1.8%) pathogenetic or likely pathogenetic (class I-II) and variants of uncertain significance (VUS) (class III) BRCA1/2 molecular alterations, respectively. HRD score was positive in 48 out of 112 (42.8%) HGSOC patients.
Conclusions. HRD testing is a reliable method for the clinical management of HGSOC patients.
Introduction
To date, ovarian cancer (OC) consists of most leading cause of death, worldwide, among gynecological malignancies 1. In particular, high-grade serous ovarian cancer (HGSOC), mostly diagnosed in advanced stage (II-IV) in accordance with The International Federation of Gynecology and Obstetrics (FIGO) classification system, is affected by unfavorable prognosis and worst clinical outcome 2. In this scenario, optimized therapeutic strategies play a pivotal role in the clinical management of HGSOC patients. Nowadays, platinum-based chemotherapy in combination with surgery is considered the standard of care for the routine management of OC patients 3. In the last years, precision medicine has revolutionized the landscape of clinically available treatments for HGSOC patients 4. Among these, poly (ADP-ribose) polymerase (PARP) inhibitors (PARPIs) emerged as novel targeted approach for HGSOC patients defective in homologous recombination repair (HRR) system 5-7. Firstly, PARPi were approved by international societies for the treatment of platinum-sensitive HGSOC patients showing germline or somatic BRCA1/2 pathogenetic alterations 8,9. Of note, activity of the HRR depends on a plethora of equally crucial actors involved, like BRCA1/2, in maintenance of DNA integrity 10,11. In this regard,, functional defects in HRR proteins, classified as homologous recombination deficiency (HRD) status, activate error-prone DNA repair mechanisms laying the basis for genomic instability and evolutionary neoplastic cell transformation 12) Clinical trials investigated the role of HRD status for the stratification of HGSOC patients electing to PARPi administration. It has been certainly showed that HRD positive HGSOC patients had a favorable clinical outcome in comparison with HRR-proficient tumors 12-14. Remarkably, HRD status is measured by bioinformatic tools able to calculate “genomic scar” from next generation sequencing (NGS) data integrating loss of heterozygosity (LOH), telomeric allelic imbalance (TAI) and large-scale state transitions (LST) 15-17. Regarding technical aspects, NGS platforms that allow molecular analysis of comprehensive genomic regions, measure HRD score integrating optimized bioinformatic algorithm 15. In fact, PARPi registrative clinical trials evaluated BRCA1/2 molecular alterations and HRD score adopting an outsourcing approach based on centralized molecular testing 13,14. However, a not-negligible rejection rate (5-25%), extensive turnaround time (TAT) and the lack of standardized preanalytical procedures dramatically impacts on the molecular testing of HRD score on diagnostic routine samples 18,19. In this scenario, commercially available diagnostic assays have been developed to implement in-house HRD testing as a partially resolutive strategy to improve the success rate of HRD molecular analysis 19. Being affected by technical and analytical pitfalls, harmonized analytical workflows and data interpretating system are required to definitively implement this diagnostic strategy in clinical practice 18-20. Not surprisingly, our Molecular Predictive Pathology Laboratory at the Department of Public Health of the University of Naples Federico II routinely adopts in-house NGS assays for BRCA1/2 and HRD evaluation on diagnostic routine specimens from HGSOC patients. Here, we review our molecular records from NGS analysis of HGSOC patients inspected for clinically relevant BRCA1/2 variants and HRD status evaluation. To clinically validate our diagnostic workflow, molecular data were also matched with clinical outcomes in a representative series of HGSOC patients.
Study design
From May 2023 to January 2024 molecular records from 147 HGSOC patients simultaneously tested for BRCA1/2 pathogenetic alterations and HRD measurement were retrieved from internal archive of University of Naples Federico II. For each patient a formalin fixed paraffin embedded (FFPE) representative of tumor lesion was available for molecular analysis adopting a commercially available NGS assay (Amoy Diagnostics Co Ltd, Xiamen, Fujian, China) integrating BRCA1/2 clinically informative molecular alterations and HRD measurement. Written informed consent was acquired from all patients and documented according to “The Italian Data Protection Authority” (http://www.garanteprivacy.it/web/guest/home/docweb/-/docwebdisplay/export/2485392). All information regarding human material was managed using anonymous numerical codes and all samples were handled in compliance with the Helsinki Declaration (http://www.wma.net/en/30publications/10policies/b3/).
Material and methods
For each patient, a series of four unstained slides (5 μm), matched with hematoxylin/eosin (H/E) stained slide representative of tumor lesion, were prepared to perform nucleic acid purification. An expert pathologist internally reviewed each case counting neoplastic cell percentage available to extract nucleic acids. Briefly, DNA extraction was realizing using QiAmp Mini Kit (Qiagen, Hilden, Germany) following manufacturer’s instructions. Two platforms were used to evaluate DNA concentration: Qubit fluorimeter 2.0 (Thermofisher Scientifics, Waltham, Massachusetts, USA) and TapeStation 4200 (Agilent, Santa Clara, California, USA) in accordance with technical guidelines 22) In particular, TapeStation 4200 (Agilent, Santa Clara, California, USA) also enabled to calculate DNA integrity number (DIN), reflecting fragmentation index of nucleic acids 22. NGS analysis was carried out adopting the Amoy HRD focus panel (Amoy Diagnostics Co Ltd, Xiamen, Fujian, China) on NextSeq 550 Dx system (Illumina, San Diego, USA). This panel includes SNVs and indels in coding/noncoding regions from 27 HRR-related genes plus hot spot mutations in 5 tumor informative genes among solid tumor patients. Halo-shape Annealing and Defer-Ligation Enrichment systems, derived from Molecular Inversion Probe (MIP) technology, were used for selecting target regions on genomic DNA. An optimized workflow was implemented batching 8 samples in each run to improve the success rate of molecular analysis on scant diagnostic samples. After DNA extension, circular DNA was repaired by manufacturer ligase enzyme and then cleaved by exonucleases in order to create single strand DNA for templating and sequencing procedures on NextSeq 550 Dx platform (Illumina, San Diego, USA). Data processing, BRCA1/2 variants and HRD scoring (GSS score) was approached on proprietary analysis software. In particular, GSS score greater than or equal to 50 revealed HRD positive status, in accordance with manufacturer procedures. Technically relevant quality metrics (median coverage, alignment percentage, BRCA medium effective depth, SNP medium effective depth, SNP uniformity) were manually inspected stratifying samples in accordance with the technical requirement of molecular testing. Briefly, if samples failed in a single quality metrics, the molecular report was successfully accepted; if 2 ≥ quality metrics < 4 were failed molecular results were classified as “suboptimal” whereas samples affected by 4 not surpassing quality metrics were diagnosed as “failed”.
Results
Overall, 2 out of 147 (1.3%) diagnostic specimens were diagnosed as inadequate after morphological evaluation. In the remaining cases, our internally optimized NGS based workflow was able to successfully carry out n = 112 out of 145 (77.2%) molecular analyses both for HRD scoring and BRCA1/2 in diagnostic routine HGSOC patients. By considering technical parameters, a neoplastic cell percentage median value of 56.0 % (ranging from 10.0 to 90.0%) were calculated to recover nucleic acids for molecular testing. In addition, nucleic acid purification yielded a median value of 40.0 ng/μL (ranging from 1.3 to 60.0 ng/μL). Moreover, DNA concentration was also estimated by adopting TapeStation 4200 (Agilent) in 96 out of 112 (85.7%). In this series, nucleic acids showed a median value of 28.5 ng/μL (ranging from 3.2 to 120.0 ng/μL). DIN was successfully calculated in each instance highlighting a median value of 3.2 (ranging from 1.4 to 6.3) (Tab. I). Overall, a median coverage of 99.8 % (ranging from 98.4 to 100.0%), alignment percentage of 96.2% (ranging from 78.1 to 99.0 %), BRCA medium effective depth of 1329.7 (ranging from 124.0 to 4699.0) BRCA uniformity of 98,6% (ranging from 92.5 to 100.0%), SNP medium effective depth of 187.7 (ranging from 16.0 to 570.0) and SNP uniformity of 93.4% (ranging from 86.7 to 97.0%) were identified (Tab. II). As showed by NGS analysis, 7 out of 112 (6.2%) and 2 out of 112 (1.8%) HGSOC patients harbored pathogenetic or likely pathogenetic (class I-II) and Variants of Uncertain Significance (VUS) (class III) BRCA1/2 molecular alterations, respectively, in accordance with AMP/CAP/ASCO/ACMG international guidelines 21. Among BRCA1/2 mutated patients, 4 out of 9 (44.4%) and 5 out of 9 (55.6%) mutated displayed BRCA1 and BRCA2 molecular alterations, respectively. In detail, 4 out of 9 (44.4%) and 5 out of 9 (55.6%) single nucleotide variants (SNVs) and small deletions or insertions were detected. A single alteration was detected in a BRCA1 non-coding region. In addition, HRD measurement highlighted a positive GS score in 48 out of 112 (42.8%) HGSOC patients (Tab. III).
Sixteen out of 147 patients who underwent testing for BRCA1/2 pathogenic alterations and HRD measurement were referred to the Oncology Department of our University Hospital for clinical care. The baseline characteristics of these patients are detailed in Table IV. The median age at diagnosis was 61 years. All patients were diagnosed with HGSOC. One patient had FIGO stage I disease, while 11 patients had stage III, and four had stage IV. In the context of surgical treatment, 9 patients received primary debulking surgery (PDS), while 4 underwent interval debulking surgery (IDS) after receiving 3 cycles of neoadjuvant platinum-based chemotherapy and 3 after 6 cycles of platinum-based chemotherapy. Among the six patients whose chemotherapy response scores (CRS) were evaluated, three exhibited a minimal tumor response (CRS1), one displayed a partial tumor response (CRS2), and two achieved a complete tumor response (CRS3). The surgical outcomes were as follows: no residual disease (R0) in twelve patients, tumor residue of less than one centimeter (R1) in two, and tumor residue of greater than one centimeter (R2) in two others. All patients received chemotherapy comprising carboplatin AUC5 + paclitaxel 175 mg/m2 every 21 days for a total of six cycles. Among the 16 patients, 15 underwent maintenance therapy, with three receiving bevacizumab, five receiving olaparib, six receiving niraparib, and one receiving olaparib in combination with bevacizumab. Currently, the maturation of survival events has not yet reached a level that would allow for the identification of relationships between particular clinical features and oncological results.
Discussion
The rapidly evolving scenario of predictive biomarkers lay the basis for novel therapeutic algorithm in the management of HGSOC patients in clinical practice 2,23. BRCA1/2 pathogenic alterations select HGSOC patients to PARPi administration stratifying patients that could benefit from a targeted approach 3-9. In the last years, HRD status has been elected as integrating biomarker able to identify HGSOC patients administrable with PARPi. Several clinical trials highlighted a statistically significant favorable outcome in HGSOC patients under PARPi administration demonstrating the clinical efficacy of BRCA1/2-HRD molecular analysis in a diagnostic routine setting. To date, HRD status is calculated by externalized NGS based assays able to measure genomic scar integrating molecular hallmarks behind DNA instability. In particular, outsourced diagnostic strategies are affected by high turnaround time (TAT), low sustainable technical cost and a non-negligible rejection rate (30.0-40.0%) drastically reducing the widespread diffusion of externalized systems in diagnostic routine practice. In this regard, a plethora of commercially available NGS assays measuring HRD score may be adopted to internally carry out HRD analysis in institutions involved in precision medicine. Despite the lack of clinical validation, the implementation of in-house HRD testing strategies overcomes technical and logistic issues of externalized testing approaches reducing rejection rate and TAT 19. Start new paragraph we overviewed our diagnostic workflow for detecting BRCA1/2 clinically informative alterations and calculating HRD score in a retrospective series of HGSOC patients by a commercially available NGS assay. Interestingly, 112 out of 145 (77.2%) HGSOC patients were successfully analyzed for both BRCA1/2 and HRD status suggesting an adequate successful rate of molecular profiling in a series of real-world samples. In addition, our approach successfully detected clinically impactful BRCA1/2 mutations in 8.0% of HGSOC patients. Among them, 6.2% (7 out of 112) and 1.8% (2 out of 112) cases revealed BRCA class I-II and class III molecular alterations, respectively. Moreover, HRD status was detected in 42.8% (48 out of 112) patients. In this scenario, pre-analytical procedures of managing diagnostic specimens dramatically impact their suitability for molecular profiling. Regarding median DIN value, microfluidic system listed successfully tested HGSOC patients in A (1 < DIN < 2), B (2≤DIN < 3) and C (3≤DIN) groups (Supplementary Table I). Interestingly, samples affected by > 4 did not surpass quality metrics; 2 ≥ quality metrics < 4 failed matched with group A and B, respectively, while diagnostic samples with optimal technical parameters were listed in group C (Supplementary Table I) (Fig. 1). The latest point strongly suggests the central role of optimized preanalytical management of diagnostic routine samples to improve the success rate in of HGSOC patients. Interestingly, NGS failed samples highlighted a median DIN value of 1.7 (ranging from 1.0 to 4.1) demonstrating the central role of pre-analytical procedures to maintain DNA integrity (Supplementary Table II) (Supplementary material) 24.
In conclusion, we evaluated a referral laboratory experience on integrated BRCA1/2-HRD molecular analysis in unselected HGSOC patients from our diagnostic routine practice supporting the key role of in-house comprehensive NGS analysis to decrease the rejection rate and TAT to optimize the clinical stratification of HGSOC patients. Further studies are recommended to clinically validate these technical strategies matching molecular and clinical records from a large cohort of HGOSC patients eligible for molecular analysis for PARPi administration.
CONFLICT OF INTEREST STATEMENT
F.P. has relevant relationship (advisory fees, honoraria, travel accommodation and expenses, grants and non-financial support) with Menarini, Roche unrelated to the current work. U.M. has received personal fees (as consultant and/or speaker bureau) from Boehringer Ingelheim, Roche, MSD, Amgen, Thermo Fisher Scientifics, Eli Lilly, Diaceutics, GSK, Merck and AstraZeneca, Janssen, Diatech, Novartis and Hedera unrelated to the current work. G.T. reports personal fees (as speaker bureau or advisor) from Roche, MSD, Pfizer, Boehringer Ingelheim, Eli Lilly, BMS, GSK, Menarini, AstraZeneca, Amgen and Bayer, unrelated to the current work. M.B. has received honoraria for consulting, advisory role, speakers’ bureau, travel, accommodation, expenses from MSD Oncology, Roche/Genetech, Astra Zeneca, Thermofisher Scientific, GSK and Illumina unrelated to the current work.
FUNDING
The Italian Health Ministry’s research program (ID: NET-2016-02363853). National Center for Gene Therapy and Drugs based on RNA Technology MUR-CN3 CUP E63C22000940007 to DS.
ETHICAL CONSIDERATION
All information regarding human material was managed using anonymous numerical codes, and all samples were handled in compliance with the Helsinki Declaration.
AUTHORS CONTRIBUTION
Conceptualisation: FP, GR, GT, UM. Methodology: all authors. Software: all authors. Validation: all authors. Formal analysis: all authors. Investigation: all authors. Resources: all authors. Data curation: all authors. Writing—original draft preparation: FP, GR, Writing—review and editing: all authors. Visualisation: all authors. Supervision: UM, GT. Project administration: UM and GT. Funding acquisition: GT, UM
Supplementary material
PRE-ANALYTICAL PROTOCOL (PART I)
Cold ischemia covering the timing gap tissue surgical remotion and fixation procedure may impact on morphological and molecular evaluation of tissue samples. Particularly, Neutral buffered formalin (NBF) fixation should be approached within 6 h from surgery to reduce the ischemic process and drastically decrease degradation rate of nucleic acids (DNA >24 h, RNA >12 h). NBF penetrate tissues at 1 mm/h and should be adopted within 24 h after dilution to 4% w/v). Remarkably, longer fixation time (DNA>72 h, RNA>48 h) also increases degradation rate of nucleic acids drastically impacting on the successful implementation of molecular techniques on over-fixed diagnostic routine samples. Although formalin fixed paraffin embedding (FFPE) tissue preserving approach represents the most common strategy to collect tissue specimens in diagnostic routine setting. It has been recommended to maintain paraffin at 56°C during tissue inclusion and archive FFPE samples <15°C.
PRE-ANALYTICAL PROTOCOL (PART II)
Neoplastic cell percentage should be ≥25.0-30.0% to successfully elect FFPE samples to molecular test. After DNA extraction, input recommendation is defined by technical specification of each assay (e.g. Amoy HRD focus panel requires almost 50 ng to successfully carry out molecular analysis). In terms of nucleic acids fragmentation, TapeStation 4200 (Agilent) platform highlighted that samples are grouped as follows inspecting DNA integrity number (DIN):
- 0<DIN<2= samples failed to NGS analysis; >4 quality checks do not meet technical cut-off (median coverage, alignment percentage, BRCA medium effective depth, SNP medium effective depth, SNP uniformity)
- 2<DIN<3= samples were suboptimal to NGS analysis; 2< quality checks <4 do not meet technical cut-off (median coverage, alignment percentage, BRCA medium effective depth, SNP medium effective depth, SNP uniformity)
- DIN >3= samples were successfully analyzed on NGS analysis; quality checks >4 meet technical cut-off (median coverage, alignment percentage, BRCA medium effective depth, SNP medium effective depth, SNP uniformity)
ID | DIN | N° of Not Optimal Analytical Metrics | |
---|---|---|---|
Group A | 81 | 1.0 | 5 |
86 | 1.0 | 5 | |
69 | 1.1 | 5 | |
75 | 1.3 | 5 | |
33 | 1.4 | 2 | |
63 | 1.4 | Failed analysis | |
64 | 1.4 | 4 | |
65 | 1.4 | 6 | |
79 | 1.4 | 5 | |
83 | 1.4 | 4 | |
84 | 1.4 | 5 | |
29 | 1.5 | 1 | |
37 | 1.5 | 4 | |
52 | 1.5 | 6 | |
77 | 1.5 | 5 | |
82 | 1.5 | 5 | |
7 | 1.6 | 4 | |
68 | 1.6 | 5 | |
3 | 1.7 | 4 | |
16 | 1.7 | 2 | |
67 | 1.7 | 5 | |
40 | 1.8 | 4 | |
50 | 1.8 | 2 | |
1 | 1.9 | 4 | |
27 | 1.9 | 1 | |
57 | 1.9 | 1 | |
71 | 1.9 | 3 | |
Group B | 28 | 2.0 | 3 |
43 | 2.0 | 1 | |
55 | 2.0 | 3 | |
56 | 2.0 | 5 | |
58 | 2.0 | 2 | |
66 | 2.0 | Failed analysis | |
73 | 2.0 | 2 | |
74 | 2.0 | 2 | |
11 | 2.1 | 1 | |
48 | 2.1 | 2 | |
8 | 2.2 | 2 | |
10 | 2.2 | 1 | |
44 | 2.2 | 4 | |
146 | 2.2 | 1 | |
5 | 2.3 | 1 | |
9 | 2.3 | 2 | |
13 | 2.3 | 2 | |
35 | 2.3 | 1 | |
6 | 2.4 | 1 | |
15 | 2.4 | 1 | |
17 | 2.4 | 0 | |
30 | 2.4 | 1 | |
45 | 2.4 | 1 | |
47 | 2.4 | 1 | |
53 | 2.4 | 1 | |
54 | 2.4 | 1 | |
18 | 2.5 | 0 | |
41 | 2.5 | 1 | |
61 | 2.5 | 3 | |
70 | 2.5 | 0 | |
80 | 2.5 | 4 | |
106 | 2.5 | 2 | |
21 | 2.6 | 1 | |
23 | 2.6 | 0 | |
31 | 2.6 | 1 | |
38 | 2.6 | 1 | |
39 | 2.6 | 1 | |
140 | 2.6 | 0 | |
147 | 2.6 | 5 | |
24 | 2.7 | 2 | |
25 | 2.7 | 1 | |
34 | 2.7 | 1 | |
49 | 2.7 | 1 | |
78 | 2.7 | 1 | |
95 | 2.7 | 0 | |
135 | 2.7 | 2 | |
2 | 2.8 | 1 | |
4 | 2.8 | 1 | |
20 | 2.8 | 0 | |
36 | 2.9 | 1 | |
76 | 2.9 | 2 | |
110 | 2.9 | 1 | |
Group C | 32 | 3.0 | 1 |
42 | 3.0 | 0 | |
46 | 3.0 | 1 | |
51 | 3.0 | 0 | |
125 | 3.0 | 0 | |
136 | 3.0 | 0 | |
12 | 3.1 | 0 | |
26 | 3.1 | 1 | |
132 | 3.1 | 1 | |
141 | 3.1 | 0 | |
59 | 3.2 | 2 | |
131 | 3.2 | 1 | |
104 | 3.3 | 0 | |
127 | 3.3 | 3 | |
138 | 3.3 | 0 | |
14 | 3.4 | 0 | |
22 | 3.4 | 1 | |
142 | 3.4 | 1 | |
134 | 3.5 | 0 | |
94 | 3.6 | 0 | |
62 | 3.7 | 3 | |
91 | 3.7 | 0 | |
100 | 3.7 | 1 | |
139 | 3.7 | 1 | |
92 | 3.8 | 0 | |
137 | 4.0 | 0 | |
109 | 4.1 | 5 | |
19 | 4.2 | 0 | |
144 | 4.3 | 1 | |
115 | 4.4 | 0 | |
118 | 4.4 | 1 | |
130 | 4.6 | 0 | |
114 | 4.7 | 0 | |
143 | 4.7 | 0 | |
145 | 4.7 | 0 | |
120 | 5.0 | 0 | |
102 | 5.5 | 0 | |
133 | 5.5 | 0 | |
117 | 5.7 | 0 | |
108 | 6.0 | 2 | |
124 | 6.0 | 1 | |
98 | 6.1 | 0 | |
122 | 6.1 | 0 | |
128 | 6.3 | 0 | |
129 | 6.3 | 0 | |
Abbreviations: DIN (DNA Integrity number). |
ID | CN% | Histological Diagnosis | DIN | ng/μl (TapeStation 4200) | ng/μl (Qubit) |
1 | 20% | HGSOC | 1.9 | 7.3 | 0.9 |
3 | 60% | HGSOC | 1.7 | 5.3 | 1.3 |
7 | 20% | HGSOC | 1.6 | 4.0 | 0.5 |
37 | 90% | HGSOC | 1.5 | 4.6 | 17.0 |
40 | 60% | HGSOC | 1.8 | 2.7 | 9.2 |
44 | 20% | HGSOC | 2.2 | 9.4 | 2.9 |
52 | 40% | HGSOC | 1.5 | 5.4 | 1.8 |
55 | 60% | HGSOC | 2.0 | 13.5 | 28.2 |
56 | 60% | HGSOC | 2.0 | 7.7 | 18.6 |
60 | 20% | HGSOC | - | 0.8 | 0.6 |
63 | 20% | HGSOC | 1.4 | 1.5 | 0.6 |
64 | 50% | HGSOC | 1.4 | 7.3 | 30.1 |
65 | 15% | HGSOC | 1.4 | 4.3 | 2.0 |
66 | 30% | HGSOC | 2.0 | 4.1 | 1.4 |
67 | 15% | HGSOC | 1.7 | 2.9 | 0.2 |
68 | 20% | HGSOC | 1.6 | 4.3 | 1.0 |
69 | 50% | HGSOC | 1.1 | 3.2 | 0.6 |
71 | 20% | HGSOC | 1.9 | 5.7 | 1.5 |
75 | 50% | HGSOC | 1.3 | 3.7 | 0.2 |
77 | 40% | HGSOC | 1.5 | 4.4 | 4.1 |
79 | 25% | HGSOC | 1.4 | 4.9 | 1.5 |
80 | 30% | HGSOC | 2.5 | 4.2 | 2.4 |
81 | 40% | HGSOC | 1.0 | 2.5 | 2.6 |
82 | 80% | HGSOC | 1.5 | 6.1 | 2.1 |
83 | 80% | HGSOC | 1.4 | 6.4 | 1.4 |
84 | 90% | HGSOC | 1.4 | 3.3 | 11.4 |
86 | 25% | HGSOC | 1.0 | 3.3 | 0.6 |
89 | 70% | HGSOC | NA | NA | 5.8 |
109 | 70% | HGSOC | 4.1 | 2.8 | 2.2 |
112 | 70% | HGSOC | - | 1.3 | 0.8 |
116 | 70% | HGSOC | NA | NA | 0.5 |
126 | 30% | HGSOC | NA | NA | 0.6 |
147 | 60% | HGSOC | 2.6 | 3.1 | 2.6 |
History
Received: September 24, 2025
Accepted: November 24, 2025
Figures and tables
Figure 1. Exemplificative grouping (A, B, C) system to distinguish samples on the basis of technical parameters: DNA fragmentation index and NGS quality check drastically impacts the failure rate of molecular testing.
ID | NC% | DIN | ng/μl (TapeStation 4200) | ng/μl (Qubit) |
---|---|---|---|---|
1 | 20% | 1.9 | 7.3 | 0.9 |
2 | 60% | 2.8 | 29.8 | 60.0 |
3 | 60% | 1.7 | 5.3 | 1.3 |
4 | 70% | 2.8 | 45.8 | 60.0 |
5 | 20% | 2.3 | 8.2 | 3.2 |
6 | 30% | 2.4 | 20.8 | 26.2 |
7 | 20% | 1.6 | 4.0 | 0.5 |
8 | 30% | 2.2 | 12.7 | 12.9 |
9 | 70% | 2.3 | 13.5 | 19.8 |
10 | 60% | 2.2 | 19.4 | 39.4 |
11 | 20% | 2.1 | 6.5 | 15.9 |
12 | 40% | 3.1 | 21.1 | 58.0 |
13 | 70% | 2.3 | 11.8 | 9.2 |
14 | 40% | 3.4 | 17.7 | 35.6 |
15 | 30% | 2.4 | 16.6 | 25.0 |
16 | 30% | 1.7 | 4.4 | 1.3 |
17 | 60% | 2.4 | 9.7 | 34.9 |
18 | 70% | 2.5 | 28.2 | 59.0 |
19 | 70% | 4.2 | 96.0 | 60.0 |
20 | 60% | 2.8 | 19.9 | 38.5 |
21 | 50% | 2.6 | 5.5 | 4.3 |
22 | 30% | 3.4 | 11.4 | 16.7 |
23 | 70% | 2.6 | 61.9 | 60.0 |
24 | 20% | 2.7 | 7.3 | 7.2 |
25 | 80% | 2.7 | 7.8 | 13.3 |
26 | 60% | 3.1 | 20.7 | 32.0 |
27 | 60% | 1.9 | 12.7 | 2.9 |
28 | 40% | 2.0 | 8.9 | 3.0 |
29 | 30% | 1.5 | 4.9 | 6.0 |
30 | 60% | 2.4 | 9.1 | 24.3 |
31 | 60% | 2.6 | 88.3 | 51.0 |
32 | 60% | 3.0 | 45.7 | 40.9 |
33 | 30% | 1.4 | 6.8 | 5.8 |
34 | 80% | 2.7 | 51.0 | 36.4 |
35 | 60% | 2.3 | 48.9 | 42.0 |
36 | 60% | 2.9 | 15.7 | 25.3 |
37 | 90% | 1.5 | 4.6 | 17.0 |
38 | 70% | 2.6 | 40.0 | 44.2 |
39 | 60% | 2.6 | 9.7 | 5.9 |
40 | 60% | 1.8 | 2.7 | 9.2 |
41 | 50% | 2.5 | 25.3 | 39.0 |
42 | 80% | 3.0 | 94.5 | 60.0 |
43 | 60% | 2.0 | 9.0 | 5.1 |
44 | 20% | 2.2 | 9.4 | 2.9 |
45 | 30% | 2.4 | 19.9 | 11.7 |
46 | 30% | 3.0 | 20.5 | 29.3 |
47 | 20% | 2.4 | 16.2 | 11.4 |
48 | 60% | 2.1 | 24.8 | 40.9 |
49 | 50% | 2.7 | 49.4 | 45.4 |
50 | 70% | 1.8 | 36.1 | 37.2 |
51 | 70% | 3.0 | 60.2 | 56.0 |
52 | 40% | 1.5 | 5.4 | 1.8 |
53 | 70% | 2.4 | 20.8 | 25.2 |
54 | 50% | 2.4 | 33.0 | 43.5 |
55 | 60% | 2.0 | 13.5 | 28.2 |
56 | 60% | 2.0 | 7.7 | 18.6 |
57 | 70% | 1.9 | 8.5 | 39.0 |
58 | 60% | 2.0 | 25.7 | 51.0 |
59 | 30% | 3.2 | 3.8 | 3.3 |
60 | 20% | - | 0.8 | 0.6 |
61 | 10% | 2.5 | 13.7 | 11.0 |
62 | 50% | 3.7 | 16.4 | 21.6 |
63 | 20% | 1.4 | 1.5 | 0.6 |
64 | 50% | 1.4 | 7.3 | 30.1 |
65 | 15% | 1.4 | 4.3 | 2.0 |
66 | 30% | 2.0 | 4.1 | 1.4 |
67 | 15% | 1.7 | 2.9 | 0.2 |
68 | 20% | 1.6 | 4.3 | 1 |
69 | 50% | 1.1 | 3.2 | 0.6 |
70 | 75% | 2.5 | 17.4 | 19.9 |
71 | 20% | 1.9 | 5.7 | 1.5 |
72 | 70% | Inadequate | ||
73 | 40% | 2.0 | 6.5 | 4.6 |
74 | 75% | 2.0 | 13.2 | 19.2 |
75 | 50% | 1.3 | 3.7 | 0.2 |
76 | 90% | 2.9 | 5.1 | 7.5 |
77 | 40% | 1.5 | 4.4 | 4.1 |
78 | 90% | 2.7 | 24.1 | 38.4 |
79 | 25% | 1.4 | 4.9 | 1.5 |
80 | 30% | 2.5 | 4.2 | 2.4 |
81 | 40% | 1.0 | 2.5 | 2.6 |
82 | 80% | 1.5 | 6.1 | 2.1 |
83 | 80% | 1.4 | 6.4 | 1.4 |
84 | 90% | 1.4 | 3.3 | 11.4 |
85 | 5% | Inadequate | ||
86 | 25% | 1.0 | 3.3 | 0.6 |
87 | 70% | NA | NA | 37.9 |
88 | 80% | NA | NA | 15.5 |
89 | 70% | NA | NA | 5.8 |
90 | 70% | NA | NA | 14.0 |
91 | 60% | 3.7 | 42.6 | 60.0 |
92 | 70% | 3.8 | 33.4 | 48.0 |
93 | 70% | NA | NA | 60.0 |
94 | 60% | 3.6 | 10.6 | 39.5 |
95 | 40% | 2.7 | 87.8 | 60.0 |
96 | 80% | NA | NA | 60.0 |
97 | 60% | NA | NA | 34.4 |
98 | 20% | 6.1 | 19.8 | 11.8 |
99 | 70% | NA | NA | 60.0 |
100 | 40% | 3.7 | 15.0 | 16.4 |
101 | 10% | NA | NA | 39.5 |
102 | 30% | 5.5 | 20.4 | 11.6 |
103 | 80% | NA | NA | 37.3 |
104 | 40% | 3.3 | 28.8 | 25.0 |
105 | 50% | NA | NA | 25.0 |
106 | 70% | 2.5 | 3.2 | 30.7 |
107 | 20% | NA | NA | 5.0 |
108 | 60% | 6.0 | 11.6 | 2.2 |
109 | 70% | 4.1 | 2.8 | 2.2 |
110 | 60% | 2.9 | 34.3 | 47.9 |
111 | 60% | NA | NA | 45.9 |
112 | 70% | - | 1.3 | 0.8 |
113 | 50% | NA | NA | 60.0 |
114 | 70% | 4.7 | 37.4 | 8.7 |
115 | 50% | 4.4 | 41.1 | 35.3 |
116 | 70% | NA | NA | 0.5 |
117 | 60% | 5.7 | 28.8 | 60.0 |
118 | 90% | 4.4 | 12 | 43.2 |
119 | 60% | NA | NA | 31.5 |
120 | 60% | 5.0 | 105.0 | 60.0 |
121 | 60% | NA | NA | 38.7 |
122 | 60% | 6.1 | 14.0 | 24.0 |
123 | 70% | NA | NA | 43.8 |
124 | 50% | 6.0 | 14.6 | 19.4 |
125 | 50% | 3.0 | 85.5 | 24.9 |
126 | 30% | NA | NA | 0.6 |
127 | 60% | 3.3 | 22.0 | 6.9 |
128 | 90% | 6.3 | 88.3 | 60.0 |
129 | 60% | 6.3 | 30.2 | 60.0 |
130 | 30% | 4.6 | 21.4 | 23.1 |
131 | 70% | 3.2 | 30.6 | 30.0 |
132 | 40% | 3.1 | 3.7 | 5.8 |
133 | 40% | 5.5 | 29.6 | 28.2 |
134 | 70% | 3.5 | 14.7 | 30.3 |
135 | 70% | 2.7 | 17.2 | 40.7 |
136 | 80% | 3.0 | 47.9 | 43.8 |
137 | 70% | 4.0 | 108.0 | 60.0 |
138 | 30% | 3.3 | 11.8 | 6.64 |
139 | 70% | 3.7 | 9.5 | 11.1 |
140 | 40% | 2.6 | 7.9 | 8.6 |
141 | 70% | 3.1 | 120.0 | 58.0 |
142 | 80% | 3.4 | 19.9 | 33.2 |
143 | 90% | 4.7 | 94.2 | 60.0 |
144 | 70% | 4.3 | 10.1 | 22.4 |
145 | 70% | 4.7 | 10.3 | 28.2 |
146 | 70% | 2.2 | 10.7 | 14.7 |
147 | 60% | 2.6 | 3.1 | 2.6 |
Abbreviations: DIN (DNA Integrity Number); HGSOC (High-Grade Serous Ovarian Cancer); NA (Not Assessed); NC% (Neoplastic Cells Percentage); ng (nanograms); μl (microliters). |
ID | Production | Total Reads | Coverage | BRCA Effective Depth | BRCA Uniformity | SNP Effective Depth | SNP Uniformity |
---|---|---|---|---|---|---|---|
2 | 2.16G | 19913472 | 99.9% | 817 | 100.0% | 164 | 96.1% |
4 | 2.01G | 18571616 | 99.9% | 979 | 100.0% | 189 | 96.4% |
5 | 1.73G | 16474232 | 99.8% | 435 | 99.2% | 66 | 92.1% |
6 | 2.03G | 18367404 | 99.9% | 778 | 99.6% | 100 | 94.5% |
8 | 1.74G | 17425778 | 99.4% | 174 | 95.7% | 33 | 90.3% |
9 | 1.72G | 21884288 | 99.8% | 388 | 95.7% | 98 | 91.3% |
10 | 1.75G | 21398172 | 99.9% | 582 | 99.6% | 80 | 93.7% |
11 | 5.52G | 50918844 | 99.9% | 511 | 99.2% | 79 | 94.1% |
12 | 4.62G | 41335728 | 99.9% | 2827 | 100.0% | 427 | 96.9% |
13 | 3.99G | 37815908 | 99.6% | 152 | 97.6% | 28 | 93.7% |
14 | 4.33G | 38975284 | 99.9% | 2661 | 98.8% | 323 | 95.8% |
15 | 3.84G | 34455110 | 99.9% | 1154 | 99.6% | 148 | 95.2% |
16 | 3.94G | 36940658 | 98.4% | 124 | 96.5% | 19 | 89.8% |
17 | 4.58G | 41698228 | 99.9% | 871 | 99.6% | 219 | 95.8% |
18 | 4.34G | 39156410 | 99.9% | 2158 | 100.0% | 277 | 96.1% |
19 | 3.72G | 33514812 | 99.9% | 2587 | 99.6% | 295 | 96.2% |
20 | 4.09G | 37142410 | 99.9% | 1067 | 100.0% | 177 | 95.9% |
21 | 4.31G | 38692248 | 99.9% | 725 | 96.9% | 96 | 90.8% |
22 | 4.72G | 41886534 | 99.9% | 1259 | 99.2% | 133 | 91.3% |
23 | 4.52G | 40647830 | 99.9% | 1364 | 100.0% | 229 | 96.5% |
24 | 4.76G | 42715040 | 99.8% | 660 | 96.9% | 92 | 89.9% |
25 | 4.64G | 41669086 | 99.9% | 921 | 98.4% | 164 | 93.0% |
26 | 4.58G | 41224262 | 99.9% | 1359 | 99.6% | 191 | 94.5% |
27 | 4.31G | 38829700 | 99.8% | 502 | 97.2% | 75 | 91.6% |
28 | 4.51G | 41530520 | 99.7% | 270 | 96.1% | 65 | 89.1% |
29 | 4.55G | 42401678 | 99.8% | 422 | 99.2% | 50 | 95.7% |
30 | 4.53G | 40806372 | 99.9% | 1422 | 99.2% | 191 | 93.6% |
31 | 4.70G | 42825632 | 99.9% | 1203 | 99.2% | 170 | 95.2% |
32 | 4.96G | 44837466 | 99.9% | 1330 | 100.0% | 178 | 95.1% |
33 | 4.44G | 43733852 | 99.5% | 171 | 99.6% | 26 | 92.7% |
34 | 4.58G | 41035748 | 99.9% | 1046 | 98.0% | 155 | 94.3% |
35 | 4.42G | 40583668 | 99.9% | 773 | 99.6% | 117 | 93.7% |
36 | 4.64G | 42201522 | 99.9% | 817 | 100.0% | 70 | 94.7% |
38 | 4.43G | 40157424 | 99.9% | 838 | 99.6% | 120 | 94.4% |
39 | 3.90G | 35460700 | 99.7% | 698 | 96.5% | 76 | 90.3% |
41 | 4.82G | 43868824 | 99.9% | 813 | 99.2% | 126 | 95.5% |
42 | 4.42G | 40131068 | 99.9% | 1100 | 100.0% | 208 | 95.8% |
43 | 4.36G | 40299812 | 99.8% | 398 | 98.4% | 51 | 94.0% |
45 | 4.84G | 43556400 | 99.9% | 840 | 97.2% | 144 | 93.9% |
46 | 4.56G | 40586888 | 99.9% | 1299 | 98.8% | 116 | 92.4% |
47 | 4.91G | 44813608 | 99.8% | 402 | 96.1% | 81 | 91.4% |
48 | 4.84G | 44602962 | 99.9% | 393 | 98.0% | 86 | 92.4% |
49 | 4.80G | 43460562 | 99.9% | 916 | 99.6% | 152 | 94.8% |
50 | 4.55G | 42126022 | 99.9% | 183 | 99.6% | 62 | 95.9% |
51 | 4.84G | 43737052 | 99.9% | 1289 | 98.8% | 210 | 93.8% |
53 | 3.89G | 35529636 | 99.9% | 695 | 99.6% | 121 | 92.9% |
54 | 3.47G | 31529008 | 99.9% | 1197 | 98.8% | 145 | 93.9% |
57 | 4.12G | 37473492 | 99.9% | 1209 | 99.6% | 119 | 95.1% |
58 | 4.28G | 39907842 | 99.9% | 241 | 99.6% | 57 | 94.4% |
59 | 3.96G | 37690392 | 99.7% | 446 | 97.2% | 60 | 89.7% |
61 | 3.94G | 36170532 | 99.8% | 766 | 92.5% | 123 | 86.8% |
62 | 3.95G | 35957586 | 99.9% | 1144 | 94.5% | 145 | 89.0% |
70 | 4.20G | 39425048 | 99.9% | 1079 | 99.2% | 140 | 94.5% |
73 | 4.16G | 45260928 | 99.7% | 227 | 97.2% | 45 | 90.5% |
74 | 3.85G | 37880930 | 99.8% | 201 | 99.6% | 48 | 95.7% |
76 | 3.81G | 40714262 | 99.6% | 308 | 98.8% | 46 | 90.1% |
78 | 4.00G | 37271824 | 99.9% | 818 | 99.6% | 113 | 95.7% |
87 | 5.14G | 49678042 | 99.9% | 2512 | 98.4% | 426 | 91.4% |
88 | 4.51G | 49024584 | 99.9% | 657 | 94.1% | 205 | 86.7% |
90 | 5.87G | 64179792 | 99.9% | 1027 | 100.0% | 218 | 96.0% |
91 | 5.49G | 48952474 | 99.9% | 3709 | 100.0% | 394 | 95.4% |
92 | 5.35G | 48318194 | 99.9% | 2158 | 99.6% | 358 | 93.2% |
93 | 4.98G | 45098256 | 99.9% | 2689 | 98.0% | 401 | 95.7% |
94 | 5.31G | 47609376 | 99.9% | 2228 | 100.0% | 302 | 94.7% |
95 | 5.33G | 47799930 | 99.9% | 4533 | 100.0% | 570 | 96.5% |
96 | 4.34G | 38893156 | 99.9% | 2326 | 100.0% | 328 | 95.4% |
97 | 4.62G | 41774942 | 99.9% | 1173 | 99.6% | 205 | 95.6% |
98 | 4.64G | 41099162 | 99.9% | 2559 | 97.2% | 243 | 90.9% |
99 | 4.41G | 41545088 | 99.8% | 158 | 100.0% | 41 | 94.0% |
100 | 4.55G | 41198850 | 99.9% | 1818 | 96.5% | 231 | 88.8% |
101 | 4.08G | 36706560 | 99.9% | 3064 | 99.2% | 381 | 94.7% |
102 | 4.25G | 38271362 | 99.9% | 1974 | 98.0% | 280 | 92.6% |
103 | 4.01G | 36258236 | 99.9% | 2374 | 99.6% | 350 | 95.6% |
104 | 4.32G | 39507416 | 99.9% | 2375 | 100.0% | 295 | 95.8% |
105 | 4.14G | 37751412 | 99.9% | 455 | 98.8% | 88 | 93.9% |
106 | 3.24G | 33789398 | 99.3% | 135 | 100.0% | 16 | 93.6% |
107 | 3.94G | 35958628 | 99.9% | 961 | 98.8% | 93 | 94.7% |
108 | 3.81G | 35128618 | 99.6% | 299 | 99.2% | 28 | 93.3% |
110 | 4.41G | 39832638 | 99.9% | 869 | 99.6% | 120 | 93.8% |
111 | 4.23G | 38265164 | 99.9% | 1167 | 98.8% | 184 | 93.7% |
113 | 4.47G | 40114626 | 99.9% | 4699 | 99.2% | 459 | 94.1% |
114 | 4.15G | 37610246 | 99.9% | 1030 | 98.4% | 165 | 90.2% |
115 | 4.06G | 36741122 | 99.9% | 1538 | 97.6% | 316 | 91.0% |
117 | 5.08G | 46050092 | 99.9% | 1876 | 99.2% | 357 | 91.7% |
118 | 4.61G | 40677240 | 99.8% | 991 | 96.5% | 134 | 89.3% |
119 | 3.57G | 32267578 | 99.9% | 1321 | 98.4% | 173 | 93.8% |
120 | 5.12G | 46101768 | 99.9% | 2055 | 96.9% | 283 | 92.2% |
121 | 5.02G | 44891200 | 99.9% | 1063 | 97.2% | 162 | 92.7% |
122 | 4.35G | 38847036 | 99.9% | 2741 | 96.9% | 328 | 90.2% |
123 | 4.84G | 43528842 | 99.9% | 2614 | 98.8% | 358 | 93.0% |
124 | 5.23G | 46709206 | 99.9% | 3116 | 94.5% | 342 | 88.8% |
125 | 3.44G | 31432526 | 99.9% | 1323 | 99.2% | 233 | 93.3% |
127 | 3.77G | 34286630 | 99.7% | 746 | 94.9% | 87 | 89.0% |
128 | 4.91G | 44385696 | 99.9% | 2716 | 100.0% | 401 | 95.7% |
129 | 5.11G | 45898028 | 99.9% | 3621 | 99.6% | 424 | 94.0% |
130 | 6.52G | 58638886 | 99.9% | 3283 | 99.2% | 346 | 95.5% |
131 | 5.00G | 45451438 | 99.9% | 1054 | 100.0% | 161 | 94.5% |
132 | 4.91G | 45782918 | 99.7% | 553 | 96.5% | 59 | 90.5% |
133 | 4.11G | 37079280 | 100.0% | 2798 | 99.6% | 283 | 94.7% |
134 | 4.19G | 37691494 | 99.9% | 1912 | 99.6% | 225 | 92.8% |
135 | 5.06G | 45640186 | 99.9% | 980 | 93.7% | 110 | 94.0% |
136 | 5.14G | 46451684 | 99.9% | 1514 | 100.0% | 199 | 95.8% |
137 | 5.55G | 50133706 | 99.9% | 3069 | 100.0% | 475 | 97.0% |
138 | 5.17G | 46407322 | 99.9% | 1748 | 97.6% | 223 | 92.8% |
139 | 4.91G | 44130552 | 99.9% | 1188 | 98.8% | 188 | 94.2% |
140 | 4.68G | 42457358 | 99.9% | 1024 | 99.2% | 223 | 93.9% |
141 | 5.37G | 48704618 | 99.9% | 2282 | 100.0% | 420 | 95.9% |
142 | 4.34G | 39721426 | 99.9% | 909 | 100.0% | 127.5 | 94.0% |
143 | 4.04G | 36819558 | 100.0% | 1355 | 99.6% | 278.94 | 94.4% |
144 | 4.20G | 39062230 | 99.9% | 748.3 | 98.0% | 115.66 | 92.7% |
145 | 4.16G | 38568320 | 99.9% | 1229 | 99.2% | 211.52 | 92.9% |
146 | 4.41G | 42489920 | 99.8% | 600 | 97.2% | 81.23 | 89.2% |
ID | BRCA Alteration | GSscore |
---|---|---|
2 | WT | 5.2 |
4 | WT | 5.7 |
5 | WT | 2.5 |
6 | WT | 28.4 |
8 | WT | 13.2 |
9 | WT | 99.5 |
10 | WT | 7.9 |
11 | WT | 4.3 |
12 | WT | 28.0 |
13 | WT | 5.1 |
14 | WT | 10.9 |
15 | WT | 19.3 |
16 | WT | 66.6 |
17 | WT | 95.9 |
18 | WT | 26.2 |
19 | WT | 98.6 |
20 | WT | 35.8 |
21 | WT | 99.5 |
22 | WT | 9.6 |
23 | WT | 71.6 |
24 | WT | 3.4 |
25 | WT | 66.3 |
26 | WT | 90.5 |
27 | WT | 3.0 |
28 | WT | 81.5 |
29 | BRCA1 intron 13 c.4358-31_4358-27del:p.? | 3.0 |
30 | WT | 34.2 |
31 | WT | 21.1 |
32 | WT | 84.9 |
33 | WT | 3.1 |
34 | WT | 95.0 |
35 | WT | 79.2 |
36 | WT | 72.9 |
38 | WT | 9.5 |
39 | WT | 3.2 |
41 | BRCA 2 exon 17 c.7887G > A:p.(W2629*):p.(Trp2629Ter) | 18.1 |
42 | WT | 11.1 |
43 | WT | 95.5 |
45 | WT | 88.6 |
46 | WT | 71.0 |
47 | WT | 2.1 |
48 | WT | 53.3 |
49 | WT | 30.3 |
50 | WT | 77.8 |
51 | WT | 99.7 |
53 | WT | 75.4 |
54 | WT | 30.0 |
57 | WT | 96.9 |
58 | WT | 94.1 |
59 | WT | 7.5 |
61 | WT | 2.0 |
62 | WT | 1.7 |
70 | WT | 41.2 |
73 | WT | 6.5 |
74 | BRCA2 exon 11 c.5433_5434delinsTT: p.(E1811_E1812delinsD*):p.(Glu1811_Glu1812delinsAspTer) | 26.6 |
76 | WT | 7.0 |
78 | WT | 99.4 |
87 | WT | 95.4 |
88 | WT | 98.7 |
90 | WT | 2.2 |
91 | WT | 43.5 |
92 | WT | 34.8 |
93 | WT | 93.8 |
94 | WT | 23.9 |
95 | WT | 95.1 |
96 | WT | 66.8 |
97 | WT | 5.3 |
98 | WT | 1.0 |
99 | VUS BRCA1 exon 9 c.964G > A p.Ala322Thr 19,84% | 10.0 |
100 | WT | 99.7 |
101 | WT | 4.0 |
102 | WT | 98.8 |
103 | WT | 23.3 |
104 | BRCA1 exon 9 c.3229_3229delAG p.Gly1077Ala fs Ter8 | 95.8 |
105 | WT | 6.6 |
106 | BRCA2 exon 23 VUS c.9006A > T; p.Glu3002Asp | 4.7 |
107 | WT | 21.8 |
108 | WT | 0.9 |
110 | WT | 13.8 |
111 | WT | 72.0 |
113 | WT | 93.9 |
114 | WT | 25.2 |
115 | WT | 99.0 |
117 | WT | 98.1 |
118 | WT | 99.4 |
119 | WT | 35.2 |
120 | WT | 23.5 |
121 | WT | 75.3 |
122 | WT | 64.3 |
123 | WT | 99.5 |
124 | WT | 94.6 |
125 | VUS BRCA1 exon 23 c.5504G > A, p.R183Q | 91.5 |
127 | WT | 3.4 |
128 | WT | 1.7 |
129 | WT | 34.2 |
130 | WT | 0.9 |
131 | WT | 31.5 |
132 | WT | 3.6 |
133 | WT | 77.1 |
134 | BRCA2 exon 21 p.A2915Vfs*12:p.Ala2915ValfsTer12 | 96.7 |
135 | WT | 11.0 |
136 | WT | 1.4 |
137 | WT | 30.3 |
138 | WT | 11.0 |
139 | WT | 8.5 |
140 | WT | 17.4 |
141 | WT | 81.0 |
142 | WT | 20.5 |
143 | WT | 86.2 |
144 | WT | 80.8 |
145 | WT | 100.0 |
146 | BRCA2 exon 18 c.8184del:p.(K2729Rfs*4):p.(Lys2729ArgfsTer4) | 85.7 |
Abbreviations: BRCA (Breast Related Cancer Antigens); GSS (Genomic Scar Score); VUS (Variants of Uncertain Significance); WT (Wild-Type). |
Characteristics | N = 16 |
---|---|
Median age | 61.0 (45-82) |
ECOG | |
· 0 | 13 |
· 1 | 3 |
Primary tumor location | |
· Ovary | 16 |
· Fallopian tube | 0 |
· Peritoneum | 0 |
FIGO stage | |
· I-II | 1 |
· III | 11 |
· IV | 4 |
Histological Subtype | |
· Serous | 16 |
· Endometroid | 0 |
Surgery | |
· PDS | 9 |
· IDS after 3 cycles | 4 |
· IDS after 6 cycles | 3 |
CRS | |
· 1 | 3 |
· 2 | 1 |
· 3 | 2 |
· Unknown | 1 |
Residual disease | |
· R0 | 12 |
· R1 | 2 |
· R2 | 2 |
Serum CA125 level | |
· Normal | 7 |
· Elevated | 9 |
BRCA1/2 status | |
· Wild type | 15 |
· BRCA1 | 1 |
· BRCA2 | 0 |
HRD status | |
· Positive (GSS > 50) | 8 |
· Negative (GSS < 50) | 8 |
Maintenance therapy | |
· Bevacizumab | 3 |
· Olaparb | 5 |
· Niraparib | 6 |
· Olaparb + Bevacizumab | 1 |
· None | 1 |
BMI | |
· < 18.5 | 1 |
· 18.5-24.99 | 7 |
· 25.0-29.99 | 3 |
· ≥30 | 5 |
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