Comprehensive genomic profiling

We run three tiers, and the choice depends on the question and on the material available.

Focused. For the common actionable drivers. Fast, material-sparing, sufficient when a particular agent is under discussion or an approval requires the detection of a specific alteration.

Broad. Covers the actionable landscape of solid tumours. The standard route when the question is open but not boundless.

Comprehensive. More than 500 genes, DNA and RNA, plus the genomic signatures that are treatment-decisive in their own right: homologous recombination deficiency, tumour mutational burden, microsatellite instability — all in one workflow, from a single material input. For advanced disease after the standard is exhausted, for rare entities, for CUP syndrome.

The comprehensive tier too is a targeted panel, not a whole genome. We do not perform whole-exome or whole-genome sequencing. This is a deliberate decision: a curated panel delivers a robust, clinically placed statement for every alteration it covers, whereas the whole genome produces a flood of variants without consequence for action. Where the question goes beyond 500 genes, we say so and refer on.

To place the methods: the detection limit for point mutations and small insertions or deletions is four percent allele frequency, ten percent in homopolymeric regions. HRD determination combines pathogenic BRCA1/2 variants with a measure of genomic instability. The concordance between the broad and the comprehensive panel is high for pathogenic and likely pathogenic variants in the overlapping genes — in an independent analysis of ovarian carcinomas. For concordance against orthogonal methods, vendor figures range between 94 and 97 percent; these figures are not independently validated.

Two things decide success or failure: the decalcification and the quantity. Decalcified material we can generally process, provided it was EDTA-decalcified — EDTA spares the nucleic acids, whereas strong acids fragment them. Fixation time is not an exclusion criterion; whether the material holds up shows in our quality control.

The input is modest: the focused and the broad panel work with 20 nanograms each of DNA and RNA, the comprehensive panel with 30. That can usually be obtained even from fine-needle biopsies.

For determining homologous recombination deficiency, a tumour-cell content of at least 30 percent is needed. But you need not worry about it: we enrich the tumour fraction by manual microdissection. Judging which area of the specimen goes in is our task, not yours.