Multi-omics analysis in suspected hereditary breast and ovarian cancer cases reveals novel candidate susceptibility factors.

Multi-omics analysis (WGS, WTS, optical genome mapping, mobile elements) in HBOC patients without core-gene variants; integration of a polygenic score

More than 80% of patients meeting hereditary breast and ovarian cancer (HBOC) criteria carry no pathogenic variant in BRCA1, BRCA2 and other core genes. The authors study 134 patients using WGS, whole-transcriptome sequencing, optical genome mapping and mobile element analysis. (Likely) pathogenic DNA-repair variants are identified in 18 patients, including several RECQ helicases, an intragenic FANCM deletion and six rare mobile element insertions. Adding a polygenic score (PRS306) shifts estimated breast cancer risk by ≥5 percentage points in a subset of women, both upward and downward.

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

A good illustration of the value of a multi-omics approach for the 'missing heritability' of HBOC, capturing structural, intronic and mobile-element variants invisible to standard panels. The factors remain candidates and the PRS is not yet clinic-ready, but the underlying message — moving beyond targeted panels toward WGS/transcriptome — is sound.

Analysis by Dr Thibaut Benquey