https://orcid.org/0000-0001-5326-1931
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Abstract
Introduction
Methylated circulating tumour DNA (ctDNA) blood tests for BCAT1/IKZF1 (COLVERA) and SEPT9 (Epi proColon) are used to detect colorectal cancer (CRC). However, there are no ctDNA assays approved for other gastrointestinal adenocarcinomas. We aimed to characterize BCAT1, IKZF1 and SEPT9 methylation in different gastrointestinal adenocarcinoma and non-gastrointestinal tumours to determine if these validated CRC biomarkers might be useful for pan-gastrointestinal adenocarcinoma detection.
Methods
Tissue DNA methylation data from colorectal (COAD, READ), gastroesophageal (ESCA, STAD), pancreatic (PAAD) and cholangiocarcinoma (CHOL) adenocarcinoma cohorts within The Cancer Genome Atlas were used for differential methylation analyses. Clinicodemographic predictors of BCAT1, IKZF1 and SEPT9 methylation, and the selectivity of hypermethylated BCAT1, IKZF1 and SEPT9 for colorectal adenocarcinomas in comparison to other cancers were each explored with beta regression.
Results
Hypermethylated BCAT1, IKZF1 and SEPT9 were each differentially methylated in colorectal and gastroesophageal adenocarcinomas. IKZF1 was differentially methylated in pancreatic adenocarcinoma. Hypermethylated DNA biomarkers BCAT1, IKZF1 and SEPT9 were largely stable across different stages of disease and were highly selective for gastrointestinal adenocarcinomas relative to other cancer types.
Discussion
Existing CRC methylated ctDNA blood tests for BCAT1/IKZF1 and SEPT9 might be usefully repurposed for use in other gastrointestinal adenocarcinomas and warrant further prospective ctDNA studies.
Acknowledgements
The authors would like to thank sample donors and The Cancer Genome Atlas Research Network for access to study data.
Funding
The author(s) reported there is no funding associated with the work featured in this article.
Disclosure statement
G.P.Y. reports personal fees from Clinical Genomics Inc, NJ, USA. E.L.S. reports grants from Clinical Genomics outside of the submitted work. No disclosures were reported by the other authors.
Author contributions
Conceptualization: Ganessan Kichenadasse, Graeme P. Young, Erin L. Symonds, Jean M. Winter; Methodology: Geraldine Laven-Law, Jean M. Winter; Formal analysis and investigation: Geraldine Laven-Law; Writing - original draft preparation: Geraldine Laven-Law; Writing - review and editing: Ganessan Kichenadasse, Graeme P. Young, Erin L. Symonds, Jean M. Winter; Supervision: Erin L. Symonds, Jean M. Winter.
Ethics approval and consent to participate
All deidentified data used in this study obtained from a publicly accessible database. Ethical approval to conduct the observations within this study is not required.
Data availability
All data used in this study was publicly accessible. Analyzed data and code that supports the findings presented in this study are available from the corresponding author upon reasonable request.