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Ovarian High-Grade Serous Carcinoma

Ovarian High-Grade Serous Carcinoma Manual Research Notes

Manual MONDO:0005211

Ovarian High-Grade Serous Carcinoma Manual Research Notes

Date: 2026-04-12

Scope

This note distills the literature and modeling decisions used for the kb/disorders/Ovarian_High-Grade_Serous_Carcinoma.yaml curation.

Cancer Modeling Decisions

  • Applied issue #1198 guidance before rewriting the disease entry.
  • Kept one disease-level mechanism graph for HGSOC instead of splitting BRCA-associated, HRD-positive, or platinum-response contexts into separate dismech pages.
  • Kept the disease anchor MONDO-first. OLS search returned MONDO:0005211 (ovarian serous adenocarcinoma) as the closest MONDO concept, but not a separate high-grade ovarian serous MONDO leaf.
  • Used NCIT to recover oncology specificity where the schema supports it: NCIT:C105555 Ovarian High Grade Serous Adenocarcinoma for disease-alignment context, NCIT:C213446 High Grade Serous Adenocarcinoma and NCIT:C126449 Serous Tubal Intraepithelial Carcinoma for histopathology, and NCIT drug/biomarker terms for olaparib, bevacizumab, carboplatin, paclitaxel, HRD, CCNE1 amplification, CA-125, and HE4.
  • Treated subtype handling as a flat facet axis rather than as separate causal programs. In the YAML, BRCA-associated versus BRCA-wild-type HGSOC is represented as a disease facet inside one graph, not as separate disease pages. I did not force a subtype_term for the BRCA-associated facet once review confirmed that MONDO:0003582 denotes a predisposition syndrome rather than a carcinoma subtype.
  • Kept pathophysiology nodes atomic. The old entry bundled origin, TP53, HRD, and genomic instability into broad blocks; the revised entry separates tubal origin, early TP53-mutant precursor state, STIC, HRD, copy-number instability, and CCNE1-linked replication stress.
  • Important schema constraint: the current dismech schema exposes MONDO/ICD disease mapping containers, but not a dedicated ncit_mappings disease slot. Because of that, NCIT disease alignment is recorded in the curation notes and expressed structurally through histopathology, biomarker, regimen, and therapeutic-agent terms.

Ontology Grounding Used

  • Disease anchor: MONDO:0005211 ovarian serous adenocarcinoma
  • Disease-level oncology counterpart: NCIT:C105555 Ovarian High Grade Serous Adenocarcinoma
  • Precursor lesion: NCIT:C126449 Serous Tubal Intraepithelial Carcinoma
  • Defining histology: NCIT:C213446 High Grade Serous Adenocarcinoma
  • Key biomarker state: NCIT:C120465 Homologous Recombination Deficiency
  • Key copy-number biomarker: NCIT:C36682 CCNE1 Gene Amplification
  • Candidate regimen concept not retained in final YAML because the current RegimenTerm enum rejected it during validation: NCIT:C63402 Carboplatin/Paclitaxel Regimen

Primary Claims Used In YAML

1. Tubal origin and precursor sequence

  • PMID:33011111 supports the tubal-origin model and the TP53-to-STIC-to-HGSOC sequence.
  • Used for:
  • tubal cell-of-origin node
  • TP53 as earliest recurrent lesion
  • STIC as precursor histopathology and pathophysiology node
  • Evidence type in YAML: OTHER
  • This paper is a review/synthesis, not a direct cohort study.

2. Near-universal TP53 mutation and core genomic architecture

  • PMID:21720365 (TCGA) remains the foundational human study for HGSOC.
  • Used for:
  • TP53 near-universality
  • HRD in about half of tumors
  • recurrent BRCA1/2 alteration
  • recurrent CCNE1 amplification
  • focal copy-number burden
  • Evidence type in YAML: HUMAN_CLINICAL
  • The study is based on clinically annotated human HGSOC tumors.

3. Pre-ciliated tubal epithelial susceptibility

  • PMID:39366996 adds recent mechanistic depth beyond the older secretory-cell-only origin model.
  • Used for:
  • the atomic node describing a cancer-prone pre-ciliated tubal epithelial state
  • Evidence type in YAML: MODEL_ORGANISM
  • The key mechanistic evidence is mouse-based lineage tracing and transformation work.

4. Copy-number-driven disease framing

  • PMID:36804485 gives a compact recent synthesis of the defining HGSOC genomic pattern: universal TP53 alteration plus widespread copy-number change.
  • Used for:
  • the copy-number-driven chromosomal instability node
  • Evidence type in YAML: OTHER
  • This paper is a review.

5. Clinical presentation and first-line management context

  • PMID:40690248 is a recent JAMA review of ovarian cancer.
  • Used for:
  • ascites, abdominal pain, abdominal distention presentation context
  • cytoreductive surgery and carboplatin/paclitaxel first-line treatment framing
  • Evidence type in YAML: OTHER
  • The paper is a review and not HGSOC-exclusive, but it is recent and clinically aligned with HGSOC-dominant advanced ovarian cancer care.

6. Maintenance olaparib

  • PMID:36082969 (SOLO1 7-year follow-up) is the clearest long-term randomized evidence tied to the BRCA-associated HGSOC facet.
  • Used for:
  • olaparib maintenance treatment entry
  • Evidence type in YAML: HUMAN_CLINICAL

7. Bevacizumab benefit enrichment

  • PMID:36252167 (GOG-0218 validation) supports biomarker-informed bevacizumab use.
  • Used for:
  • bevacizumab treatment entry
  • Evidence type in YAML: HUMAN_CLINICAL

8. CA-125 and HE4 biomarker context

  • PMID:30917847 supports CA-125 and HE4 as practical biomarker entries.
  • Evidence type in YAML: OTHER
  • Review article summarizing diagnostic biomarker performance.

Literature Not Fully Expanded Into YAML

  • The existing research/Ovarian_High-Grade_Serous_Carcinoma-deep-research-falcon.md already captures additional 2023-2025 literature on dissemination timing, spheroid biology, and tumor microenvironment variation.
  • I did not turn every one of those claims into YAML because the issue called for a coherent disease-level curation, not a maximal import of every published HGSC detail.
  • In particular, dissemination-mode, stromal subtype, and immune-ecosystem papers were treated as background unless they cleanly sharpened an atomic disease mechanism node.

Remaining Curation Judgment Calls

  • The subtype list is intentionally narrow. Under the #1198 guidance, I did not encode multiple orthogonal axes (BRCA status, HRD status, stage, platinum sensitivity, site of spread) as if they were one subtype tree.
  • The current schema does not yet provide a structured disease-level NCIT mapping slot. If that slot is added later, NCIT:C105555 should be promoted from curation notes into a first-class disease mapping.
  • The current RegimenTerm dynamic enum also rejected NCIT:C63402 and NCIT:C160097, so the final YAML keeps oncology specificity through NCIT therapeutic agents rather than regimen descriptors.