Detection of Gastric Cancer with Novel Methylated DNA Markers: Discovery, Tissue Validation, and Pilot Testing in Plasma

Clinical Cancer Research : an Official Journal of the American Association for Cancer Research
Bradley W AndersonDavid A Ahlquist

Abstract

Purpose: Gastric adenocarcinoma is the third most common cause of cancer mortality worldwide. Accurate and affordable noninvasive detection methods have potential value for screening and surveillance. Herein, we identify novel methylated DNA markers (MDM) for gastric adenocarcinoma, validate their discrimination for gastric adenocarcinoma in tissues from geographically separate cohorts, explore marker acquisition through the oncogenic cascade, and describe distributions of candidate MDMs in plasma from gastric adenocarcinoma cases and normal controls.Experimental Design: Following discovery by unbiased whole-methylome sequencing, candidate MDMs were validated by blinded methylation-specific PCR in archival case-control tissues from U.S. and South Korean patients. Top MDMs were then assayed by an analytically sensitive method (quantitative real-time allele-specific target and signal amplification) in a blinded pilot study on archival plasma from gastric adenocarcinoma cases and normal controls.Results: Whole-methylome discovery yielded novel and highly discriminant candidate MDMs. In tissue, a panel of candidate MDMs detected gastric adenocarcinoma in 92% to 100% of U.S. and South Korean cohorts at 100% specificity. Levels of mo...Continue Reading

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Citations

Sep 6, 2019·Helicobacter·M Constanza CamargoJose C Machado
Nov 6, 2018·NPJ Precision Oncology·David A Ahlquist
Feb 6, 2020·Briefings in Bioinformatics·Jiangpeng WuShuyan Li
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Dec 17, 2020·International Journal of Molecular Sciences·María Alejandra AlarcónAlejandro H Corvalán
Feb 18, 2021·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Shounak MajumderJohn B Kisiel

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