DICER1 germline pathogenic variants cause DICER1 tumor predisposition syndrome — broad sp...
Deterministic view of the source YAML entity. Clinical authority remains with the cited source IDs and reviewer sign-off state.
| ID | BMA-DICER1-GERMLINE-PLEUROPULMONARY-BLASTOMA |
|---|---|
| Type | Actionability |
| Status | reviewed 2026-05-18 | pending_clinical_signoff | actionability review required |
| Diseases | DIS-OVARIAN |
| Sources | SRC-NCCN-PEDIATRIC-SARCOMA |
Actionability Facts
| Biomarker | BIO-DICER1-GERMLINE |
|---|---|
| Variant | DICER1 germline pathogenic (RNase IIIb domain hotspot or LoF) |
| Disease | DIS-OVARIAN |
| ESCAT tier | IIA |
| Recommended combinations | International PPB Registry consultation on first PPB suspicion (resection + adjuvant chemotherapy protocol), fertility-sparing oophorectomy for unilateral Sertoli-Leydig cell tumor in young women, thyroidectomy decision-making per multinodular goiter / nodule risk; total thyroidectomy with risk-reducing intent debated, lifestyle: smoking avoidance critical (synergistic lung-tumor risk in DICER1 carriers), DICER1 surveillance per International Consensus (Stewart et al., Clin Cancer Res 2018; AACR Pediatric Working Group 2017) |
| Evidence summary | DICER1 germline pathogenic variants cause DICER1 tumor predisposition syndrome — broad spectrum centered on pleuropulmonary blastoma (PPB) in early childhood, ovarian Sertoli-Leydig cell tumor in adolescence / young-adult females, multinodular goiter + differentiated thyroid cancer, cystic nephroma, embryonal rhabdomyosarcoma (cervix / bladder / kidney), pineoblastoma, and pituitary blastoma. Confirmed-carrier surveillance protocol (per International PPB Registry Consensus / Stewart et al. 2019 / DICER1 Cancer Predisposition Surveillance Statement): chest CT (low-dose) at age 3-6 months + 2.5 years + 8 years (PPB peak incidence < 6 years), chest X-ray q6mo to age 8 then annually to age 12, abdominal/pelvic US q6-12mo from infancy through age 8 then annual through adolescence, thyroid US q3y starting age 8, gynecologic exam + transabdominal pelvic US annual from age 8-10 (Sertoli-Leydig). Symptom-directed brain MRI for pineoblastoma / pituitary blastoma concern. Smoking avoidance is critical (synergistic lung-tumor risk). ESCAT IIA. |
Notes
STUB — Wave A+B germline expansion. Linked Indication: none (no DICER1- specific surveillance Indication exists yet). Two-Clinical-Co-Lead signoff queued. Disease anchor uses DIS-OVARIAN (Sertoli-Leydig); PPB lacks a Disease entity. Variant biology: pathognomonic dual-hit pattern with germline LoF (truncating/splice) + somatic missense in RNase IIIb hotspot (codons E1705, D1709, G1809, D1810, E1813) inside tumor — tumor sequencing alone misses the germline allele.
Used By
No reverse references found in the YAML corpus.