Tracheoesophageal and Rare Anomalies Cancer Evolution and Risk

TRACER: Tracheoesophageal and Rare Anomalies – Cancer Evolution and Risk
Every year, some babies are born with rare anatomical defects that affect how their digestive and breathing systems develop. Two such conditions are Esophageal Atresia (EA) and Tracheoesophageal Fistula (TEF)—where the esophagus and the trachea (the windpipe) fail to separate properly during early development. These conditions affect about 1 in every 3,000 births, often leading to serious challenges with feeding, breathing, and growth.
Many children with EA/TEF also have other birth defects, such as problems with the heart, kidneys, or limbs. These combinations are often seen in syndromes like VACTERL, which includes a specific set of congenital anomalies. Despite extensive medical testing, many families still don’t receive a clear genetic explanation for why these conditions occurred.  While surgery can correct the physical defects, many patients continue to face lifelong health risks. One major concern is the development of Barrett’s Esophagus (BE) in adulthood—a condition caused by chronic acid reflux that damages the esophagus and increases the risk of esophageal cancer, including Esophageal Adenocarcinoma (EAC) and Esophageal Squamous Cell Carcinoma (ESCC).
The TRACER project aims to uncover the genetic and molecular causes behind these rare conditions and provide answers for patients and families. We want to understand why these birth defects happen, whether they increase the risk of BE and esophageal cancer later in life and how we can enable early detection and personalized treatments for those at highest risk.
TRACER aims to deliver better care, clearer answers, and more effective therapies for children born with these rare but serious conditions—and to reduce their risk of developing cancer later in life.

To do this, our team is using cutting-edge technologies as long-read genome sequencing to study DNA and epigenetic changes in detail, total RNA sequencing and small molecule experiments to explore how biological processes are affected and spatial transcriptomics to map how genes behave in different regions of esophageal tissues.

By analysing tissue samples from patients with EA, BE, EAC, and ESCC—and comparing them to healthy controls—we hope to identify biomarkers: molecular signals that can help predict disease risk or guide treatment. These samples, including surgical tissue, biopsies, and patient-derived cell lines, are stored in a biobank. Clinical data is linked to genetic information in a secure database, helping researchers group patients with similar traits and search for shared genetic causes.

WAR23-37: Long-read genome sequencing to bridge the gap: missing heritability in esophageal atresia

This project is part of an ongoing collaborative endeavor of the departments of Pediatric Surgery, Obstetrics and Gynecology, Gastroenterology and Hepatology, Clinical Genetics and Cell Biology.

 

Collaborations with experts at Erasmus MC and other national and international research institutes are helping us expand the study and improve the chances of discovering meaningful patterns.

Prof. Dr. Heiko Reutter – Universitätsklinikum Erlangen, Germany
Prof. Dr.Johannes Shumacher, Universitätsklinikum Erlangen, Germany
Prof. Dr. Wendy C. Chung – Columbia University Medical Center, New York, NY, USA

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Erasmus MC Rotterdam Team
Dr. J. Vlot – Pediatric Surgeon
Dr. J.M. Schnater – Pediatric Surgeon
Dr. M.M. Alves – Functional Experiments Expert
Dr. A.S. Brooks – Clinical Geneticist
Dr. Y. van Bever – Clinical Geneticist
Prof. Dr. R.J. Rottier – Developmental Biologist
Prof. Dr. R.M.H. Wijnen – Head of Pediatric Surgery & Chairman, Sophia Children’s Hospital