Genomic Landscape of 6597 Hong Kong HBOC Patients: Implications for Beyond-BRCA Multi-Gene Panel Testing and Cancer Surveillance.

PALB2

Germline variants in predisposition genes beyond BRCA1 and BRCA2, led by PALB2, TP53, ATM and BARD1

The Hong Kong Hereditary Breast Cancer Family Registry analysed 6,597 patients recruited on family history and clinical criteria using multi-gene next-generation sequencing. Germline variants were identified in 10.9% of cases for BRCA1 and BRCA2 and in 3.5% for beyond-BRCA susceptibility genes. PALB2 was the most prevalent non-BRCA gene, followed by TP53, ATM and BARD1. New cancers or recurrences were detected during surveillance, with pick-up rates of 8.3% for PALB2, 29.4% for TP53, 33.3% for PTEN and 5.6% for BARD1. Since local testing policy does not cover beyond-BRCA genes, the authors argue for expanding the public screening framework.

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

The value of this work lies not in discovery — the non-BRCA spectrum described is the expected one — but in documenting pick-up rates under real surveillance, a figure rarely published and far more informative than carrier prevalence alone. The 3.5% of beyond-BRCA carriers account for nearly a quarter of the genetic diagnoses in this series: in a system funding only BRCA1 and BRCA2, that directly quantifies the missed opportunity. The 29.4% for TP53 and 33.3% for PTEN, however, rest on very small carrier numbers not specified in the abstract and should not be read as risk estimates.

Analysis by Dr Thibaut Benquey