Comprehensive Genomic Profiling Report

TruSight Oncology 500 — ESMO 2024 Compliant

Published

March 25, 2026

Sample: EGA_OV_TSO500_001 | Tumor: High-Grade Serous Ovarian Carcinoma (HGSOC) | Panel: TSO500 (523 genes, 1.94 Mb) | Source: EGA EGAD50000001451

1 Patient & Sample Information

Field Value
Sample ID EGA_OV_TSO500_001
Tumor Type High-Grade Serous Ovarian Carcinoma (HGSOC)
Panel TruSight Oncology 500 (TSO500)
Specimen Type FFPE Tumor Tissue
Sequencing Platform Illumina NovaSeq X
Reference Genome GRCh38 (hg38)
Institution Institution Name
Report Date 2026-03-25

2 Quality Control

Overall QC: PASS
Metric Value Threshold Status
Total Reads 45,200,000 - -
Mapped Reads 44,100,000 - -
Mapping Rate 97.6% >95% PASS
Mean Coverage 487.3x >200x PASS
On-Target Rate 92% >80% PASS
Duplicate Rate 15% <30% PASS
Tumor Purity 65% >10% PASS

2.1 Annotation Methodology

Component Tool / Database Details
Variant Calling GATK Mutect2 v4.6.1 Tumor-only mode, panel intervals
Variant Annotation Ensembl VEP (GRCh38) --everything --pick --canonical --hgvs
Transcript Database Ensembl / GENCODE canonical One consequence per variant via --pick
Functional Prediction SIFT + PolyPhen-2 Missense protein impact prediction
Population Frequency gnomAD v4.0 Germline filtering at AF >1%
Clinical Databases ClinVar + COSMIC Pathogenicity + somatic mutation catalogs
Clinical Actionability OncoKB API (live) Therapeutic levels → ESCAT tiers
Nomenclature HGVS (varnomen.hgvs.org) Protein (p.) and coding (c.) notation
CNV Detection CNVkit (hybrid mode) Panel-optimized copy number segmentation
Fusion Detection Manta SV caller Structural variants for gene fusions
Community Evidence CiVIC (civicdb.org) CiVIC GraphQL API — variant evidence, gene summaries, community-curated assertions
Oncogenicity Classification AMP/ASCO/CAP Four-Tier System Li et al., J Mol Diagn 2017; combines OncoKB + CiVIC + VEP + ClinVar evidence

3 Somatic Variants

9 somatic variants detected. Annotated with Ensembl VEP (GRCh38) using canonical transcripts and HGVS nomenclature.

Gene HGVS Protein HGVS Coding VAF Consequence Impact SIFT / PolyPhen ClinVar Classification
TP53 ENST00000269305.9 p.R248W c.742C>T 68% (156/229) missense_variant HIGH deleterious probably_damaging Pathogenic pathogenic
BRCA1 ENST00000357654.9 p.E1836fs c.5506del 42% (89/212) frameshift_variant HIGH - Pathogenic pathogenic
PIK3CA ENST00000263967.4 p.H1047R c.3140A>G 23% (52/226) missense_variant MODERATE deleterious probably_damaging Pathogenic pathogenic
NF1 ENST00000358273.9 p.R1534* c.4600C>T 31% (67/216) stop_gained HIGH - Pathogenic pathogenic
RB1 ENST00000267163.5 p.E137* c.409G>T 15% (34/227) stop_gained HIGH - Likely_pathogenic likely_pathogenic
CDK12 ENST00000447079.7 p.K765fs c.2293del 38% (82/216) frameshift_variant HIGH - Pathogenic pathogenic
PTEN ENST00000371953.8 p.R130* c.388C>T 45% (98/218) stop_gained HIGH - Pathogenic pathogenic
ARID1A ENST00000324856.14 p.Q1334* c.4000C>T 12% (28/233) stop_gained HIGH - Likely_pathogenic likely_pathogenic
KRAS ENST00000256078.10 p.G12V c.35G>T 8% (18/225) missense_variant MODERATE deleterious probably_damaging Pathogenic pathogenic

3.1 Mutation Confidence Ranking

Variants ranked by call confidence based on VAF relative to detection threshold (5%), sequencing depth, and database concordance.

Gene Alteration Confidence Rationale
TP53 p.R248W High confidence VAF 68% (>10% threshold), depth 156/229, Pathogenic
BRCA1 p.E1836fs High confidence VAF 42% (>10% threshold), depth 89/212, Pathogenic
PIK3CA p.H1047R High confidence VAF 23% (>10% threshold), depth 52/226, Pathogenic
NF1 p.R1534* High confidence VAF 31% (>10% threshold), depth 67/216, Pathogenic
RB1 p.E137* High confidence VAF 15% (>10% threshold), depth 34/227, Likely_pathogenic
CDK12 p.K765fs High confidence VAF 38% (>10% threshold), depth 82/216, Pathogenic
PTEN p.R130* High confidence VAF 45% (>10% threshold), depth 98/218, Pathogenic
ARID1A p.Q1334* High confidence VAF 12% (>10% threshold), depth 28/233, Likely_pathogenic
KRAS p.G12V Uncertain Borderline metrics: VAF 8%, depth 18/225
Questionable variants should be confirmed by orthogonal methods (Sanger, ddPCR).

3.2 VAF Distribution

4 Copy Number Alterations

Gene Type Log2 Ratio Copy Number Chromosome Start End
CCNE1 AMPLIFICATION 2.80 12 chr19 30,200,000 30,250,000
PTEN DELETION −2.10 0 chr10 87,860,000 87,970,000
BRCA1 DELETION −1.50 1 chr17 41,200,000 41,280,000
MYC AMPLIFICATION 1.90 8 chr8 128,700,000 128,770,000

4.1 Genome-Wide CNV Profile

4.2 Genomic Overview (Circos)

5 Gene Fusions

Fusion Exons Breakpoints Supporting Reads Type Known Fusion
EWSR1::FLI1 exon 7::exon 6 chr22:29,683,123 — chr11:128,675,261 45 in-frame TRUE

5.1 Fusion Visualization

6 Genomic Biomarkers

6.1 Details

6.1.1 TMB

4.6 mutations/Mb — TMB-Low

  • Variant count: 9 non-synonymous coding variants
  • Panel coding size: 1.94 Mb (TSO500)
  • Classification: TMB-High ≥10, TMB-Intermediate 6–10, TMB-Low <6

6.1.2 MSI

5.2% — MSS

  • Unstable sites: 2 / 38
  • Threshold: ≥20% for MSI-H

6.1.3 HRD

Score 58 — HRD-positive

  • LOH: 22 | TAI: 18 | LST: 18
  • Threshold: ≥42 for HRD-positive
  • Note: Panel-based estimation — confirm with dedicated HRD assay for clinical decisions.

7 Clinical Actionability (ESCAT)

Important

9 actionable alteration(s) identified (ESCAT Tier I–III) across 14 total classified alterations.

ESCAT Tier Gene Alteration Type Oncogenic Level Sources Description
I BRCA1 E1836fs mutation Likely Oncogenic LEVEL_1 OncoKB Target ready for implementation in routine clinical decisions
I BRCA1 DELETION cna Likely Oncogenic LEVEL_1 OncoKB Target ready for implementation in routine clinical decisions
II CCNE1 AMPLIFICATION cna Oncogenic LEVEL_3A OncoKB Investigational target with strong evidence; enables clinical trial enrollment
III PIK3CA H1047R mutation Oncogenic LEVEL_3B OncoKB Clinical benefit demonstrated in other tumor types or similar molecular alterations
III NF1 R1534* mutation Likely Oncogenic LEVEL_3B OncoKB Clinical benefit demonstrated in other tumor types or similar molecular alterations
III CDK12 K765fs mutation Likely Oncogenic LEVEL_3B OncoKB Clinical benefit demonstrated in other tumor types or similar molecular alterations
III PTEN R130* mutation Oncogenic LEVEL_3B OncoKB Clinical benefit demonstrated in other tumor types or similar molecular alterations
III KRAS G12V mutation Oncogenic LEVEL_3B OncoKB Clinical benefit demonstrated in other tumor types or similar molecular alterations
III PTEN DELETION cna Oncogenic LEVEL_3B OncoKB Clinical benefit demonstrated in other tumor types or similar molecular alterations
IV ARID1A Q1334* mutation Likely Oncogenic LEVEL_4 OncoKB Preclinical evidence of actionability
X TP53 R248W mutation Likely Oncogenic - OncoKB No evidence for actionability or lack of data
X RB1 E137* mutation Likely Oncogenic - OncoKB No evidence for actionability or lack of data
X MYC AMPLIFICATION cna Oncogenic - OncoKB No evidence for actionability or lack of data
X EWSR1::FLI1 EWSR1::FLI1 fusion Unknown - OncoKB No evidence for actionability or lack of data

7.1 Community Evidence (CiVIC)

No CiVIC community evidence found for the identified variants.

7.1.1 CiVIC AMP/ASCO/CAP Assertions

No CiVIC AMP/ASCO/CAP assertions found for the identified genes.

8 Oncogenicity Classification (AMP/ASCO/CAP)

AMP/ASCO/CAP Somatic Variant Classification
Gene Alteration AMP Tier AMP Level Evidence
TP53 p.R248W Tier II Level D Oncogenic (Likely Oncogenic) + HIGH VEP impact
BRCA1 p.E1836fs Tier I Level A OncoKB LEVEL_1 (FDA-approved/guideline)
PIK3CA p.H1047R Tier II Level C OncoKB LEVEL_3B (approved in different tumor type)
NF1 p.R1534* Tier II Level C OncoKB LEVEL_3B (approved in different tumor type)
RB1 p.E137* Tier II Level D Oncogenic (Likely Oncogenic) + HIGH VEP impact
CDK12 p.K765fs Tier II Level C OncoKB LEVEL_3B (approved in different tumor type)
PTEN p.R130* Tier II Level C OncoKB LEVEL_3B (approved in different tumor type)
ARID1A p.Q1334* Tier II Level D OncoKB LEVEL_4 (biological evidence)
KRAS p.G12V Tier II Level C OncoKB LEVEL_3B (approved in different tumor type)
CCNE1 p.E1 Tier III VUS Insufficient evidence for classification
Classification per Li et al., J Mol Diagn 2017; 19(1):4-23

9 Treatment-Focused Literature Evidence

Literature search identified 19 PubMed and 18 Scopus articles. Each narrative below focuses on therapeutic implications and recommended treatment strategies for the identified alterations.

9.1 TP53

TP53 R248W is classified as Likely Oncogenic in high-grade serous ovarian carcinoma. No directly targeted therapies are currently approved for this specific alteration in ovarian cancer. However, this alteration may inform prognosis and response to standard platinum-based chemotherapy. Consider enrollment in basket trials or molecular tumor boards for emerging therapeutic strategies.

References: 1. Elayapillai S et al. Potential and mechanism of mebendazole for treatment and maintenance of ovarian cancer.. Gynecologic oncology. 2021. PMID: 33131904 2. De Souza C et al. The P72R Polymorphism in R248Q/W p53 Mutants Modifies the Mutant Effect on Epithelial to Mesenchymal Transition Phenotype and Cell Invasion via CXCL1 Expression.. International journal of molecular sciences. 2020. PMID: 33126568 3. Gao F et al. A pedigree-based prediction model identifies carriers of deleterious de novo mutations in families with Li-Fraumeni syndrome.. Genome research. 2020. PMID: 32817165

9.2 BRCA1

BRCA1 E1836fs is classified as Likely Oncogenic in high-grade serous ovarian carcinoma. Recommended treatment: Based on OncoKB Level LEVEL_1 evidence, Niraparib or Olaparib or Rucaparib or Olaparib + Bevacizumab is/are indicated as standard-of-care targeted therapy for patients with this alteration. These agents have demonstrated clinical benefit in prospective trials and are FDA-approved for this indication. Investigational options: Olaparib + Abiraterone + Prednisone, Talazoparib, Talazoparib + Enzalutamide (Evidence Level: LEVEL_3B, LEVEL_3B, LEVEL_3B) represent investigational strategies with emerging evidence. Enrollment in clinical trials targeting this alteration should be considered. Treatment decisions should integrate this molecular finding with clinical context, prior therapy lines, and patient performance status.

9.3 PIK3CA

PIK3CA H1047R is classified as Oncogenic in high-grade serous ovarian carcinoma. Investigational options: Alpelisib + Fulvestrant, Capivasertib + Fulvestrant, Inavolisib + Palbociclib + Fulvestrant, RLY-2608 (Evidence Level: LEVEL_3B, LEVEL_3B, LEVEL_3B, LEVEL_4) represent investigational strategies with emerging evidence. Enrollment in clinical trials targeting this alteration should be considered. Treatment decisions should integrate this molecular finding with clinical context, prior therapy lines, and patient performance status.

References: 1. Passarelli A et al. Alpelisib for PIK3CA-mutated advanced gynecological cancers: First clues of clinical activity.. Gynecologic oncology. 2024. PMID: 38518529 2. Kashofer K, Reich O, Regauer S. Acquisition of Genetic Aberrations During the Progression of High-Grade Intraepithelial Lesions/Micro-Invasive Squamous Cancers to Widely Invasive Cervical Squamous Cell Cancer.. Archives of pathology & laboratory medicine. 2023. PMID: 36800542 3. Zundell JA et al. Targeting the IRE1α/XBP1 Endoplasmic Reticulum Stress Response Pathway in ARID1A-Mutant Ovarian Cancers.. Cancer research. 2021. PMID: 34548333

9.4 CCNE1

CCNE1 amplification is classified as Oncogenic in high-grade serous ovarian carcinoma. Investigational options: Lunresertib + Camonsertib, BLU-222, Lunresertib (Evidence Level: LEVEL_3A, LEVEL_4, LEVEL_4) represent investigational strategies with emerging evidence. Enrollment in clinical trials targeting this alteration should be considered. Treatment decisions should integrate this molecular finding with clinical context, prior therapy lines, and patient performance status.

References: 1. Blanc-Durand F et al. Early Clinical and Molecular Biomarkers in Patients With Advanced Ovarian Cancer Undergoing Neoadjuvant Chemotherapy: CHIVA Phase II GINECO Trial.. JCO precision oncology. 2026. PMID: 41533997 2. Aubuchon LN et al. Targeting ALC1 can safely expand the therapeutic utility of PARP inhibitors across high-grade serous ovarian cancers.. bioRxiv : the preprint server for biology. 2025. PMID: 41415416 3. Chang TY et al. Integrated Spatial Analysis Reveals the Molecular Landscape of Ovarian Precancerous Lesions.. Cancer research. 2025. PMID: 41411622

9.5 PTEN

PTEN deletion is classified as Oncogenic in high-grade serous ovarian carcinoma. Investigational options: Capivasertib + Fulvestrant, GSK2636771, AZD8186 (Evidence Level: LEVEL_3B, LEVEL_4, LEVEL_4) represent investigational strategies with emerging evidence. Enrollment in clinical trials targeting this alteration should be considered. Treatment decisions should integrate this molecular finding with clinical context, prior therapy lines, and patient performance status.

References: 1. Galvão JMS et al. Genomic landscape of pediatric germ cell tumors reveals oncogenic mutations and copy number alterations.. Frontiers in oncology. 2026. PMID: 41777659 2. Du M et al. Oncological Outcomes and Genomic Features of Gastric-Type Endocervical Adenocarcinoma, the Most Aggressive and Common HPV-Independent Cervical Cancer.. Cancers. 2026. PMID: 41595239 3. Chen W et al. EPI-SauriCas9-based mouse ovarian cancer models recapitulating pten deletion in patients.. Communications biology. 2025. PMID: 41466059

9.6 References

  1. Elayapillai S, et al. Potential and mechanism of mebendazole for treatment and maintenance of ovarian cancer.. Gynecologic oncology. 2021. PMID: 33131904
  2. De Souza C, et al. The P72R Polymorphism in R248Q/W p53 Mutants Modifies the Mutant Effect on Epithelial to Mesenchymal Transition Phenotype and Cell Invasion via CXCL1 Expression.. International journal of molecular sciences. 2020. PMID: 33126568
  3. Gao F, et al. A pedigree-based prediction model identifies carriers of deleterious de novo mutations in families with Li-Fraumeni syndrome.. Genome research. 2020. PMID: 32817165
  4. Sakuragi N, et al. Dominant-negative mutation of p53 tumor suppressor gene in endometrial carcinoma.. Gynecologic oncology. 2001. PMID: 11733960
  5. Passarelli A, et al. Alpelisib for PIK3CA-mutated advanced gynecological cancers: First clues of clinical activity.. Gynecologic oncology. 2024. PMID: 38518529
  6. Kashofer K, Reich O, Regauer S. Acquisition of Genetic Aberrations During the Progression of High-Grade Intraepithelial Lesions/Micro-Invasive Squamous Cancers to Widely Invasive Cervical Squamous Cell Cancer.. Archives of pathology & laboratory medicine. 2023. PMID: 36800542
  7. Zundell JA, et al. Targeting the IRE1α/XBP1 Endoplasmic Reticulum Stress Response Pathway in ARID1A-Mutant Ovarian Cancers.. Cancer research. 2021. PMID: 34548333
  8. Murakami K, et al. Frequent PIK3CA mutations in eutopic endometrium of patients with ovarian clear cell carcinoma.. Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc. 2021. PMID: 34172890
  9. Lee JB, et al. Phase 2 study of TAS-117, an allosteric akt inhibitor in advanced solid tumors harboring phosphatidylinositol 3-kinase/v-akt murine thymoma viral oncogene homolog gene mutations.. Investigational new drugs. 2021. PMID: 33723724
  10. Blanc-Durand F, et al. Early Clinical and Molecular Biomarkers in Patients With Advanced Ovarian Cancer Undergoing Neoadjuvant Chemotherapy: CHIVA Phase II GINECO Trial.. JCO precision oncology. 2026. PMID: 41533997
  11. Aubuchon LN, et al. Targeting ALC1 can safely expand the therapeutic utility of PARP inhibitors across high-grade serous ovarian cancers.. bioRxiv : the preprint server for biology. 2025. PMID: 41415416
  12. Chang TY, et al. Integrated Spatial Analysis Reveals the Molecular Landscape of Ovarian Precancerous Lesions.. Cancer research. 2025. PMID: 41411622
  13. Taylor SJ, Gourley C. Cyclin E1 as a driver of oncogenesis; high grade serous ovarian cancer as an exemplar.. Critical reviews in oncology/hematology. 2026. PMID: 41380866
  14. Jarratt A, et al. Genomics of ovarian cancers and the potential of precision medicine.. Therapeutic advances in medical oncology. 2025. PMID: 41367952
  15. Galvão JMS, et al. Genomic landscape of pediatric germ cell tumors reveals oncogenic mutations and copy number alterations.. Frontiers in oncology. 2026. PMID: 41777659
  16. Du M, et al. Oncological Outcomes and Genomic Features of Gastric-Type Endocervical Adenocarcinoma, the Most Aggressive and Common HPV-Independent Cervical Cancer.. Cancers. 2026. PMID: 41595239
  17. Chen W, et al. EPI-SauriCas9-based mouse ovarian cancer models recapitulating pten deletion in patients.. Communications biology. 2025. PMID: 41466059
  18. Vemuri A, et al. A Deeper Dive into POLE -Mutated Endometrial Carcinomas : The Contributions and Consequences of Tumor Mutational Burden.. The American journal of surgical pathology. 2026. PMID: 41436846
  19. Yang F, et al. Clinicopathological Diagnosis and Prognosis of Endometrioid Borderline Ovarian Tumors: Dual Case Reports and Literature Review.. Cancer reports (Hoboken, N.J.). 2025. PMID: 41152971

10 Coverage Gaps

10.1 Per-Gene Coverage

All genes met the minimum 200x coverage threshold.

Disclaimer: This report is generated for research purposes following ESMO 2024 guidelines. Clinical decisions should be confirmed by a certified molecular pathology laboratory. OncoKB annotations provided under academic license. ESCAT classifications per Mateo et al., Ann Oncol, 2018. CiVIC annotations sourced from the open-access community knowledgebase (civicdb.org). AMP/ASCO/CAP classification per Li et al., J Mol Diagn 2017; 19(1):4-23.

Pipeline: ngs-tertiary-analysis v0.2.0 | Reference: GRCh38 | Panel: TSO500 (523 genes, 1.94 Mb coding)