Refining neoplasm risk in DICER1-related tumor predisposition.

DICER1

Germline DICER1 pathogenic variants with moderate penetrance, predisposing to a broad spectrum of malignant and benign neoplasms

DICER1-related tumor predisposition is an autosomal dominant disorder predisposing to a broad spectrum of malignant and benign neoplasms. This retrospective study included 945 patients who underwent DICER1 genetic testing at Institut Curie (Paris) between 2012 and 2023: among 584 index cases, 91 (16%) carried a germline DICER1 pathogenic variant and 31 (5%) harbored only somatic pathogenic variants. Several tumors not previously part of the spectrum were identified: ETMR-like brain tumor and testicular Sertoli cell tumor are now recognized as DICER1-related neoplasms, and schwannoma is a strong candidate. Among 170 relatives carrying a germline pathogenic variant, the cumulative incidence of malignant neoplasms was 4.8% (95% CI: 2.1%-9.1%) at 10 years and 15.8% (95% CI: 8.9%-24.7%) at 50 years. Overall neoplasm risk was significantly higher in females, primarily driven by thyroid follicular nodular disease.

Synthesis written by Geno'X. For the full original abstract, please refer to the source publication.

Estimating risk in relatives rather than in index cases limits ascertainment bias, and these figures (15.8% malignant neoplasm risk at 50 years) support a moderate penetrance that calls for proportionate surveillance. The extended spectrum (ETMR-like tumor, testicular Sertoli cell tumor) directly affects testing indications; schwannoma, however, remains a candidate association and should not yet be added to testing criteria. The cohort is retrospective and drawn from a national referral centre: replication in other populations remains desirable.

Analysis by Dr Thibaut Benquey