Endoscopic Samples Show Precancerous Genomic Changes in Barrett's Esophagus
By LabMedica International staff writers Posted on 22 Jun 2015 |
Next-generation sequencing (NGS) has been used to detect genomic mutations in precancerous esophageal tissue, which may improve cancer surveillance and early detection in patients with Barrett's esophagus.
Barrett's esophagus (BE) develops in a subset of patients with gastroesophageal reflux disease (GERD) and can increase the risk of developing cancer of the esophagus and although periodic surveillance for cancer is recommended for BE patients; these examinations may fail to identify precancerous dysplasia and early cancers.
Scientists at Columbia University College of Physicians and Surgeons (New York, NY, USA) and their colleagues selected two groups of patients: 13 "non-progressors" who were patients with BE who never manifested dysplasia or esophageal adenocarcinoma (EAC) during at least two years of monitoring, and 15 "progressors" who were patients who developed high-grade dysplasia (HGD) or EAC, and control samples showing no evidence of Barrett's intestinal metaplasia. The investigators analyzed formalin-fixed, paraffin-embedded (FFPE) tissue samples tissue taken from esophageal biopsies or endoscopic mucosal resections.
DNA was extracted and quantitated by fluorometry with the Invitrogen Qubit fluorometer and the Invitrogen Quant-iT double-strand DNA BR Assay Kit (Life Technologies; Grand Island, NY, USA). Samples from some patients were sequenced in either Life Technologies Ion Torrent and/or MiSeq (Illumina, San Diego, CA, USA) platforms, or in parallel.
The team found that found that progressors had mutations in 75% (6/8) of cases compared to 0% in non-progressors. The tumor suppressor protein p53 (TP53) was the most commonly mutated gene in the BE progressor group. Mutations were also found in the adenomatous polyposis coli (APC) and cyclin-dependent kinase inhibitor 2A (CDKN2A) tumor suppressor genes. Next-generation sequencing from routine FFPE non-neoplastic Barrett’s esophagus samples can detect multiple mutations in minute areas of Barrett’s intestinal metaplasia (BIM) with high analytical sensitivity.
The authors concluded that that DNA from routine endoscopic FFPE samples of non-dysplastic BIM can be efficiently used to simultaneously detect multiple mutations by NGS with high analytical sensitivity, enabling the application of genomic testing of BE patients for improved HGD and EAC surveillance in clinical practice. Antonia R. Sepulveda, MD, PhD, Professor of Pathology and Cell Biology, and senior author of the study said, “The ability to detect mutations in non-neoplastic mucosa, quantitatively and with high detection sensitivity, makes it possible to use NGS mutational testing in the early detection and surveillance of patients who develop BE.” The study was published in the July 2015 issue of the Journal of Molecular Diagnostics.
Related Links:
Columbia University College of Physicians and Surgeons
Life Technologies
Illumina
Barrett's esophagus (BE) develops in a subset of patients with gastroesophageal reflux disease (GERD) and can increase the risk of developing cancer of the esophagus and although periodic surveillance for cancer is recommended for BE patients; these examinations may fail to identify precancerous dysplasia and early cancers.
Scientists at Columbia University College of Physicians and Surgeons (New York, NY, USA) and their colleagues selected two groups of patients: 13 "non-progressors" who were patients with BE who never manifested dysplasia or esophageal adenocarcinoma (EAC) during at least two years of monitoring, and 15 "progressors" who were patients who developed high-grade dysplasia (HGD) or EAC, and control samples showing no evidence of Barrett's intestinal metaplasia. The investigators analyzed formalin-fixed, paraffin-embedded (FFPE) tissue samples tissue taken from esophageal biopsies or endoscopic mucosal resections.
DNA was extracted and quantitated by fluorometry with the Invitrogen Qubit fluorometer and the Invitrogen Quant-iT double-strand DNA BR Assay Kit (Life Technologies; Grand Island, NY, USA). Samples from some patients were sequenced in either Life Technologies Ion Torrent and/or MiSeq (Illumina, San Diego, CA, USA) platforms, or in parallel.
The team found that found that progressors had mutations in 75% (6/8) of cases compared to 0% in non-progressors. The tumor suppressor protein p53 (TP53) was the most commonly mutated gene in the BE progressor group. Mutations were also found in the adenomatous polyposis coli (APC) and cyclin-dependent kinase inhibitor 2A (CDKN2A) tumor suppressor genes. Next-generation sequencing from routine FFPE non-neoplastic Barrett’s esophagus samples can detect multiple mutations in minute areas of Barrett’s intestinal metaplasia (BIM) with high analytical sensitivity.
The authors concluded that that DNA from routine endoscopic FFPE samples of non-dysplastic BIM can be efficiently used to simultaneously detect multiple mutations by NGS with high analytical sensitivity, enabling the application of genomic testing of BE patients for improved HGD and EAC surveillance in clinical practice. Antonia R. Sepulveda, MD, PhD, Professor of Pathology and Cell Biology, and senior author of the study said, “The ability to detect mutations in non-neoplastic mucosa, quantitatively and with high detection sensitivity, makes it possible to use NGS mutational testing in the early detection and surveillance of patients who develop BE.” The study was published in the July 2015 issue of the Journal of Molecular Diagnostics.
Related Links:
Columbia University College of Physicians and Surgeons
Life Technologies
Illumina
Read the full article by registering today, it's FREE!
Register now for FREE to LabMedica.com and get complete access to news and events that shape the world of Clinical Laboratory Medicine.
- Free digital version edition of LabMedica International sent by email on regular basis
- Free print version of LabMedica International magazine (available only outside USA and Canada).
- Free and unlimited access to back issues of LabMedica International in digital format
- Free LabMedica International Newsletter sent every week containing the latest news
- Free breaking news sent via email
- Free access to Events Calendar
- Free access to LinkXpress new product services
- REGISTRATION IS FREE AND EASY!
Sign in: Registered website members
Sign in: Registered magazine subscribers
Latest Molecular Diagnostics News
- Blood Proteins Could Warn of Cancer Seven Years before Diagnosis
- New DNA Origami Technique to Advance Disease Diagnosis
- Ultrasound-Aided Blood Testing Detects Cancer Biomarkers from Cells
- New Respiratory Syndromic Testing Panel Provides Fast and Accurate Results
- New Synthetic Biomarker Technology Differentiates Between Prior Zika and Dengue Infections
- Novel Biomarkers to Improve Diagnosis of Renal Cell Carcinoma Subtypes
- RNA-Powered Molecular Test to Help Combat Early-Age Onset Colorectal Cancer
- Advanced Blood Test to Spot Alzheimer's Before Progression to Dementia
- Multi-Omic Noninvasive Urine-Based DNA Test to Improve Bladder Cancer Detection
- First of Its Kind NGS Assay for Precise Detection of BCR::ABL1 Fusion Gene to Enable Personalized Leukemia Treatment
- Urine Test to Revolutionize Lyme Disease Testing
- Simple Blood Test Could Enable First Quantitative Assessments for Future Cerebrovascular Disease
- New Genetic Testing Procedure Combined With Ultrasound Detects High Cardiovascular Risk
- Blood Samples Enhance B-Cell Lymphoma Diagnostics and Prognosis
- Blood Test Predicts Knee Osteoarthritis Eight Years Before Signs Appears On X-Rays
- Blood Test Accurately Predicts Lung Cancer Risk and Reduces Need for Scans