Abstract 479P
Background
Adenomatous polyps, precursors to colorectal cancer (CRC), are currently under-diagnosed by screening methods, while their detection and removal is the key to treatment-free survival. Tissue-specific open chromatin regions (OCR) have been shown to carry tissue of origin information in plasma cell-free DNA (cfDNA), information that could be used for non-invasive diagnostics. We show here the potential of using OCR information derived from plasma cfDNA whole genome bisulfite sequencing (WGBS) data for identification of advanced adenoma patients.
Methods
OCRs previously described to be specific for small intestine in tissue were used as surrogates for establishing colorectal cancer and advanced adenoma (AA) specific regions to be evaluated in cfDNA WGBS data. 2 pooled samples from patients with advanced adenoma and 3 pooled samples from patients with stage I colorectal cancer and 5 pooled samples of control patients were used for OCR filtering and model building. AA and CRC stage I specific OCR-model validation was performed using WGBS data of cfDNA extracted from 10 individual advanced adenoma patients, serrated adenoma (N=2), tubulovillous adenoma (N=4), tubular adenoma (N=4) and 10 individual age/gender matching colonoscopy verified control patients.
Results
Initial small intestine data analysis identified 28456 OCR regions. Further filtering on WGBS data of pooled AA+CRC stage I (cases) and control samples resulted with 1074 OCR model showing maximum difference between cases and controls. Model validation on individual AA and control plasma samples resulted with 50% (5/10) of AA samples being correctly identified at 90% (9/10) specificity. Further evaluation into histological subtypes revealed that model detected 100% (2/2) serrated adenoma, 50% (2/4) tubulovillous adenoma and 25% (1/4) tubular adenoma patients, indicating potential preferential signal depending on the subtype.
Conclusions
We highlight here the potential of using open chromatin status of cfDNA for screening applications for advanced adenoma detection. Further investigation into adenoma subtypes and clinical utility in combination with other biomarkers is ongoing.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
Universal Diagnostics S.L.
Funding
Universal Diagnostics S.L.
Disclosure
P. Canal-Noguer: Full/Part-time employment: Universal Diagnostics S.L. M. Chersicola: Full/Part-time employment: Geneplanet d.o.o. K. Kruusmaa: Leadership role, Shareholder/Stockholder/Stock options, Full/Part-time employment: Universal Diagnostics S.L. M. Bitenc: Leadership role, Shareholder/Stockholder/Stock options, Full/Part-time employment, Officer/Board of Directors: Universal Diagnostics S.L.; Leadership role, Shareholder/Stockholder/Stock options, Full/Part-time employment, Officer/Board of Directors: Geneplanet d.o.o. All other authors have declared no conflicts of interest.