BCAT1, IKZF1 and SEPT9 : methylated DNA biomarkers for detection of pan-gastrointestinal adenocarcinomas

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.

Medienart:

E-Artikel

Erscheinungsjahr:

2024

Erschienen:

2024

Enthalten in:

Zur Gesamtaufnahme - year:2024

Enthalten in:

Biomarkers : biochemical indicators of exposure, response, and susceptibility to chemicals - (2024) vom: 22. Apr., Seite 1-11

Sprache:

Englisch

Beteiligte Personen:

Laven-Law, Geraldine [VerfasserIn]
Kichenadasse, Ganessan [VerfasserIn]
Young, Graeme P [VerfasserIn]
Symonds, Erin L [VerfasserIn]
Winter, Jean M [VerfasserIn]

Links:

Volltext

Themen:

Circulating tumour DNA
Colorectal cancer
DNA methylation
Diagnostic biomarkers
Gastric cancer
Journal Article
Oesophageal cancer

Anmerkungen:

Date Revised 22.04.2024

published: Print-Electronic

Citation Status Publisher

doi:

10.1080/1354750X.2024.2340663

funding:

Förderinstitution / Projekttitel:

PPN (Katalog-ID):

NLM371337364