Dit is een abstract uit de studie waarbij Exact Sciences betrokken is ivm opsporen van andere vormen van kanker:
Novel Epigenetic Markers for Detection of Esophageal Cancer: Selection by
Whole Methylome Sequencing and Tissue Validation
William R. Taylor, John B. Kisiel, Tracy C. Yab, Xiaoming Cao, Patrick Foote, Douglas W.
Mahoney, Navtej Buttar, Thomas C. Smyrk, David A. Ahlquist
Background: DNA methylation studies in esophageal adenocarcinoma (EAC) and squamous
cell carcinoma (ESCC) have primarily focused on known tumor suppressor genes. Such
efforts have yielded important mechanistic insights, but have provided few clinically useful
markers. Massively parallel sequencing technology applied across the methylome affords an
unbiased and comprehensive approach to the identification of discriminant markers for
potential application in cancer screening and diagnosis. Aims: 1) Conduct methylome-wide
discovery to identify EAC and ESCC-specific DNA methylation. 2) Select and validate top
candidate markers suitable for downstream clinical application.
Results: We identified 94 EAC
and 88 ESCC DMRs from over 25 million sequencing reads; 85% had cancer related
ontologies. From these, the top 68 (34 for each subset) were selected for MSP assay and
technical validation. After re-testing, 80% of the candidate markers matched or exceeded
their respective sequencing metrics. Several markers achieved almost perfect discrimination
for EAC. The most discriminant 18 markers were taken to biological validation; 12 achieved
superior AUC, fold change, and control group methylation (Table). Six markers demonstrated
high methylation in both tumor types; the other 6 appeared to target EAC preferentially
over ESCC. One marker in particular, FGF14, highly discriminated EAC from ESCC (Figure)
with an AUC of 0.87. Conclusion: Unbiased methylome-wide sequencing, with appropriate
filtering, yields outstanding candidate markers for detection of esophageal cancer.
Als dat verder bevestigd en officieel gevalideerd wordt dan gaan we door het dak.