Single-gene diagnostics

A comprehensive panel is not always the right route. When a particular agent is under discussion, when an approval requires the detection of a defined alteration, or when the clinical question is narrowly drawn, the focused single test is often the better choice: faster to report, sparing of the tissue, and without the incidental findings a broad panel inevitably brings.

We offer the single markers that are relevant to treatment or classification. Which route fits the specific case — a single marker or the panel after all — we clarify with you. Sometimes the honest answer is that a marker no longer suffices today and the panel serves the patient better.

Prognostic and classifying markers

POLE — endometrial cancer. A POLE mutation in the exonuclease domain marks the ultramutated, prognostically excellent group of the molecular endometrial cancer classification. It is one of the four markers that sort these tumours into POLEmut, MMR-deficient, p53-abnormal and no specific molecular profile (NSMP) — with immediate consequences for how intensively to treat in the adjuvant setting.

MLH1 and MGMT promoter. MLH1 promoter methylation, in an MMR defect, separates the sporadic case from Lynch syndrome. MGMT promoter methylation is predictive in glioblastoma for the response to temozolomide. More complex methylation analyses, for instance for CNS tumour classification, we do not offer.

The choice of method follows the marker. Point mutations, hotspots and the defined FGFR3 fusions we detect by digital or quantitative PCR — sensitive, fast and material-sparing. Microsatellite instability runs by fragment-length analysis, POLE by sequencing, the promoter methylations after bisulfite conversion by qPCR. For several predictive markers we additionally offer detection from plasma, where taking tissue again is impractical.

For all single markers, paraffin-embedded tissue suffices, as a block or as sections. Most tests are reported within five working days; POLE sequencing takes five to ten. All times count from receipt with us.

From tissue we detect variants from a fraction of five percent. This threshold is chosen deliberately and is not merely a matter of sensitivity: at the cutting board, the carry-over of the smallest amounts of foreign DNA can never be entirely excluded — pathology is not a sterile place. A threshold not driven to the technical limit guards against exactly the misinterpretation that a detection set too low would produce. From plasma, where the mutated fraction is naturally smaller, the validated limit is 0.1 percent.