Epithelial Ovarian Cancer (WHO Histotypes)

name: Epithelial Ovarian Cancer
display_name: Epithelial Ovarian Cancer (WHO Histotypes)
creation_date: "2026-06-19T00:00:00Z"
description: >-
  Epithelial ovarian cancer is not a single disease but a curated union of
  mechanistically distinct histotypes that share an ovarian/tubal epithelial
  origin and overlapping clinical presentation. The major WHO histotypes —
  high-grade serous, clear cell, endometrioid, and mucinous carcinoma — differ
  fundamentally in their precursor lesions, driver pathways, genomic stability,
  and treatment response, and are therefore modelled as separate Disease
  entries rather than bundled into one entity. This grouping records the
  histotype framework and the lump/keep-split rationale over those distinct
  entries; it replaces an earlier umbrella "ovarian adenocarcinoma" Disease
  entry, whose histotype-divergent driver biology now lives in the individual
  member entries.
grouping_basis:
- CLINICAL_CONVENTION
- SHARED_PHENOTYPE
grouping_rationale: >-
  The members are lumped only by clinical/histopathological convention (WHO
  classification of epithelial ovarian carcinoma by histotype) and shared
  anatomic site and presentation, NOT by a shared mechanism — which is exactly
  why they are kept as separate Disease entries. High-grade serous carcinoma is
  TP53-mutated, homologous-recombination-deficient (frequently BRCA1/2), and
  chromosomally unstable, arising from fallopian-tube fimbrial epithelium (STIC).
  Clear cell and endometrioid carcinomas are endometriosis-associated and
  ARID1A/PI3K-driven, with endometrioid additionally Wnt/CTNNB1-activated and
  enriched for mismatch-repair deficiency/Lynch syndrome. Mucinous carcinoma is
  KRAS-driven with a HER2/ERBB2-amplified subset and an intestinal-type,
  cystadenoma-to-carcinoma progression. Low-grade serous carcinoma (LGSC) is a
  fifth histotype — MAPK-pathway-driven (KRAS/BRAF/NRAS), TP53-wild-type,
  relatively genomically stable, and not a precursor-related variant of HGSC —
  but MONDO currently lacks a distinct LGSC class separate from the generic
  ovarian serous adenocarcinoma term (MONDO:0005211) that the HGSC entry uses;
  LGSC is therefore noted here as a future member to be added once a distinct
  entry and term are available. The membership criterion is NECESSARY (being a
  member entails primary epithelial ovarian carcinoma histotype), used to audit
  listed members; it is deliberately not SUFFICIENT because epithelial ovarian
  origin alone does not assign a specific histotype.
mappings:
  mondo_mappings:
  - term:
      id: MONDO:0002752
      label: ovarian adenocarcinoma
    mapping_predicate: skos:closeMatch
    mapping_source: MONDO
    mapping_justification: >-
      closeMatch: this grouping is the curated WHO-histotype union of epithelial
      ovarian carcinomas, closely aligned with the MONDO "ovarian adenocarcinoma"
      class but scoped to the four curated histotype member entries (plus LGSC as
      a noted future member) rather than the full MONDO descendant set.
membership_criteria:
- description: >-
    A member is a primary epithelial carcinoma of the ovary assignable to a WHO
    epithelial-ovarian-carcinoma histotype (high-grade serous, low-grade serous,
    clear cell, endometrioid, or mucinous).
  criteria_semantics: NECESSARY
  logic:
    criterion_predicate: OTHER
    description: >-
      Primary epithelial carcinoma of the ovary classified by WHO histotype.
      Carried as OTHER because the unifying feature is anatomic/histologic
      convention rather than a single shared gene, phenotype, or mechanism module.
members:
- member: Ovarian High-Grade Serous Carcinoma
  member_type: DISEASE
  differentiating_mechanisms:
  - description: >-
      Near-universal TP53 mutation with frequent homologous-recombination
      deficiency (BRCA1/2 and other HRR defects), chromosomal instability, and a
      fallopian-tube fimbrial (STIC) origin; platinum- and
      PARP-inhibitor-sensitive. The dominant histotype (~70%).
    gene:
      preferred_term: TP53
      term:
        id: hgnc:11998
        label: TP53
- member: Clear Cell Ovarian Carcinoma
  member_type: DISEASE
  differentiating_mechanisms:
  - description: >-
      ARID1A (SWI/SNF) loss and PIK3CA activation on an endometriosis-associated
      background, with typically wild-type TP53; presents early-stage but is
      relatively chemoresistant.
    gene:
      preferred_term: ARID1A
      term:
        id: hgnc:11110
        label: ARID1A
- member: Ovarian Endometrioid Carcinoma
  member_type: DISEASE
  differentiating_mechanisms:
  - description: >-
      ARID1A, PTEN, and PIK3CA alterations with distinctive Wnt/beta-catenin
      (CTNNB1) activation on an endometriosis-associated background, and frequent
      mismatch-repair deficiency/Lynch-syndrome links; generally favorable
      prognosis when low-grade.
    gene:
      preferred_term: CTNNB1
      term:
        id: hgnc:2514
        label: CTNNB1
- member: Ovarian Mucinous Carcinoma
  member_type: DISEASE
  differentiating_mechanisms:
  - description: >-
      KRAS-driven (early, frequent) with a HER2/ERBB2-amplified subset and
      intestinal-type differentiation, arising via a
      cystadenoma-to-borderline-to-carcinoma sequence; relatively resistant to
      standard platinum-taxane chemotherapy. True ovarian primaries are rare
      (many are GI metastases).
    gene:
      preferred_term: KRAS
      term:
        id: hgnc:6407
        label: KRAS