DEMO-EC-007 — ec-molsubtype

Classification result

DEMO-EC-007

moderate confidence

POLEmut

POLE exonuclease domain mutation. Best prognosis. Swedish guidelines: no adjuvant treatment for stage I-II.

Classification path

1 POLE_EDM Positive POLE p.V411L

Multiple classifier

Additional subtype features detected alongside the primary POLEmut classification:

Per the WHO 2020 hierarchy, the primary classification is POLEmut.

Secondary evidence

TMB

198.0

Concordant TMB 198.0 mut/Mb concordant with POLEmut phenotype.

CNA burden

0.0

Concordant Fraction genome altered: 0.04 — concordant with POLEmut (expected low).

Signatures

Concordant Expected signatures: SBS10a, SBS10b. Present: SBS10a, SBS10b.

Spectrum

Discordant C>A: 50.0% >= 20.0% [PASS]; T>G: 0.0% >= 4.0% [FAIL]; C>G: 8.3% <= 0.6% [FAIL]; indel_fraction: 14.3% <= 5.0% [FAIL]

Clinical notes

p.V411L is a tier1 established pathogenic hotspot.
Multiple classifier: concurrent MMRd, p53abn detected. Per WHO 2020 hierarchy, classified as POLEmut.
Concurrent MMRd evidence: MSI-H (32.0%).
Concurrent p53abn evidence: TP53 p.R273H.
POLEmut+p53abn: evidence shows prognosis follows POLEmut (León-Castillo et al. 2020). POLE status dominates.
POLEmut+MMRd: classify as POLEmut per hierarchy. Note: patient may still benefit from immunotherapy evaluation.
Swedish guidelines: no adjuvant treatment recommended for stage I-II POLEmut.