DNA Repair Synthetic-Lethality Cancers

name: DNA Repair Synthetic-Lethality Cancers
display_name: DNA Repair Synthetic-Lethality Cancers
creation_date: "2026-06-18T00:00:00Z"
description: >-
  DNA repair synthetic-lethality cancers are tumors whose mechanism graph
  includes homologous recombination or FA/BRCA pathway impairment,
  replication-associated DNA damage accumulation, and vulnerability to PARP
  inhibition and/or platinum-induced DNA lesions. The grouped entries differ in
  lineage and initiating oncogenic program, but share a therapeutically
  important DNA-repair dependency modeled by the
  dna_repair_synthetic_lethality module.
grouping_basis:
- SHARED_MECHANISM
- SHARED_TREATMENT_RESPONSE
grouping_rationale: >-
  Grouped on the shared DNA-repair synthetic-lethality mechanism: each member
  conforms to the dna_repair_synthetic_lethality module, with impaired or
  therapeutically targetable DNA damage repair creating sensitivity to PARP or
  platinum stress. The members remain separate Disease entries because their
  primary identities and initiating biology differ: Ewing sarcoma is driven by
  EWSR1-FLI1 transcriptional reprogramming, fallopian tube cancer centers on
  tubal high-grade serous precursor biology, and ovarian high-grade serous
  carcinoma combines TP53 alteration, HRD, copy-number instability, and acquired
  resistance mechanisms.
membership_criteria:
- description: >-
    A disorder belongs to this grouping if and only if it conforms to the DNA
    repair synthetic-lethality module, capturing a tumor DNA-repair defect or
    dependency that creates PARP/platinum vulnerability or related resistance
    biology.
  criteria_semantics: NECESSARY_AND_SUFFICIENT
  logic:
    criterion_predicate: CONFORMS_TO_MODULE
    module: dna_repair_synthetic_lethality
    description: >-
      Conforms to the DNA repair synthetic-lethality module.
members:
- member: Ewing Sarcoma
  member_type: DISEASE
  differentiating_mechanisms:
  - description: >-
      EWSR1-FLI1 fusion-driven chromatin and transcriptional rewiring creates a
      pediatric sarcoma context in which PARP/platinum synthetic-lethality
      biology is modeled downstream of the fusion program rather than a
      classical germline BRCA-deficient origin.
    gene:
      preferred_term: EWSR1
      term:
        id: hgnc:3508
        label: EWSR1
- member: Fallopian Tube Cancer
  member_type: DISEASE
  differentiating_mechanisms:
  - description: >-
      Fallopian tube cancer is grouped through the tubal high-grade serous
      pathway, with BRCA1/BRCA2-associated homologous recombination repair
      deficiency modeled at the fallopian tube epithelial precursor site.
    gene:
      preferred_term: BRCA1
      term:
        id: hgnc:1100
        label: BRCA1
- member: Ovarian High-Grade Serous Carcinoma
  member_type: DISEASE
  differentiating_mechanisms:
  - description: >-
      Ovarian high-grade serous carcinoma carries a mature HRD/PARP-platinum
      vulnerability and resistance model, including BRCA1/BRCA2 deficiency,
      POLQ-associated alternative repair, and restored-HRR escape.
    gene:
      preferred_term: BRCA1
      term:
        id: hgnc:1100
        label: BRCA1
notes: >-
  This grouping is intentionally therapeutic-mechanistic rather than an anatomic
  or histology grouping. It should grow by adding tumor entries that declare
  conformance to the DNA repair synthetic-lethality module.