Design and evaluation of a custom circulating tumour DNA assay to detect endometrial cancer recurrence

TL;DR

A new test was developed to detect endometrial cancer recurrence using DNA in the blood, showing high accuracy.

Contribution

A custom ctDNA assay for endometrial cancer recurrence detection was designed and validated with high sensitivity and specificity.

Findings

The ECctDNA-panel detected hotspot mutations in 100% of primary tumours tested.

The panel detected mutations at 0.74% variant allele frequency in cfDNA samples.

The assay showed 71.4% sensitivity and 96% specificity for recurrence detection.

Abstract

Circulating tumour DNA (ctDNA) has high sensitivity to detect endometrial cancer (EC) recurrence. An EC-specific ctDNA panel (ECctDNA-panel) was designed using TCGA/CPTAC mutation profile datasets and whole exome sequencing data from primary ECs. The ECctDNA-panel was tested using commercial standards to determine the detection limit for known driver variants, before investigating the plasma cell free DNA (cfDNA) from patients with/without recurrence. The ECctDNA-panel was able to detect EC hotspot mutations at >1% AF in 100% (42/42) of primary tumours tested. The ctDNA standards confirmed detection as low as 0.74% VAF in 5 ng template DNA. The ECctDNA-panel detected hotspot variants in 10/14 patients with recurrence and in 1/25 without recurrence: sensitivity/specificity 71.4%/96% and accuracy 87.2%. Potentially actionable mutations were identified in 8/10 ctDNA positive recurrences. We report the development of an ECctDNA-panel that has a high diagnostic accuracy to detect EC recurrence and could be utilised to guide patient’s further management.

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