Monoallelic BRCA1/2 variants in pediatric, adolescent, and young adult patients with central nervous system tumors.

Monoallelic germline BRCA1/BRCA2 variants as possible low-penetrance susceptibility factors.

Analysis of 367 paediatric, adolescent and young adult (AYA) patients with primary CNS tumours, all sequenced by clinical exome including BRCA1 and BRCA2. Rare germline BRCA1/2 variants were identified in 17 patients (4.6 %), of whom 5 (1.4 %) carried pathogenic or likely pathogenic variants and 12 (3.3 %) VUS. The authors conclude that monoallelic BRCA1/2 variants act as low-penetrance susceptibility factors rather than primary oncogenic drivers. Interpretation is limited by cohort heterogeneity, the lack of a control group and the absence of systematic somatic analysis.

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

The findings support including BRCA1/2 in germline panels for paediatric and AYA CNS tumours, with implications for genetic counselling and long-term surveillance. But the limitations — no controls, no analysis of loss of heterozygosity / homologous-recombination deficiency — call for caution: low-penetrance susceptibility is not causation. To be confirmed before any change in practice.

Analysis by Dr Thibaut Benquey