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Genetic Test Improves Prognosis for Esophageal Cancer

By LabMedica International staff writers
Posted on 13 Jul 2014
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Image: The Cytosponge, a non-endoscopic test for collecting cells from the esophagus, in gelatin capsule (right) and expanded (left) (Photo courtesy of Cambridge Cancer Center).
Image: The Cytosponge, a non-endoscopic test for collecting cells from the esophagus, in gelatin capsule (right) and expanded (left) (Photo courtesy of Cambridge Cancer Center).
The genetic basis of why some people with a serious complication of acid reflux known as Barrett's esophagus go on to develop esophageal cancer has been determined.

A novel noninvasive test could detect esophageal cancer much earlier, thereby improving the prognosis of what is currently a cancer with a poor survival rate. Esophageal cancer makes up about 1% of all cancers diagnosed in the USA, where estimates suggest that in 2014, about 18,170 people will discover they have the cancer, and about 15,450 will die of it.

A consortium of international scientists led by those at University of Cambridge (UK) and collaborating with the University of Southampton (UK) sequenced the DNA of patients with Barrett's esophagus and patients with esophageal cancer (EAC), and mapped out their genetic similarities and differences.

The team used a "non-endoscopic" test to identify high-risk Barrett's esophagus by retrieving cells from the affected part of the esophagus that could then be checked for presence of the mutated genes. The "non-endoscopic" test is called the cytosponge, or "sponge-on-a-string" test, and involves the patient swallowing a capsule containing a sponge attached to a thread. When the capsule reaches the stomach it dissolves, releasing the sponge, which collects cells from the esophagus wall as it is pulled out by the clinician or nurse.

Mutation validation was performed in a cohort of 90 EACs and 109 Barrett's esophagus biopsies, including 43 Barrett's esophagus biopsies with histopathologically confirmed high-grade dysplasia (HGD) and 66 with no dysplasia. The Access Array microfluidics polymerase chain reaction (PCR) platform (Fluidigm; South San Francisco, CA, USA) together with high-throughput sequencing (Illumina; San Diego, CA, USA) was used for targeted resequencing.

The scientists found mutations in the genes tumor protein 53 (TP53) and SMAD family member 4 (SMAD4) that offered a way of identifying patients in which Barrett's esophagus is progressing into cancer. Although the cytosponge is still under development, the investigators believe it could be used to look for mutations in TP53 and SMAD4 to identify patients with early stage esophageal cancer.

There are two types of esophageal cancer, adenocarcinoma and squamous cell carcinoma. People with Barrett's esophagus, a condition that can develop from prolonged, untreated acid reflux or heartburn have a higher risk of developing adenocarcinoma of the esophagus. Tim Underwood, MBBS, PhD, FRCS, a clinician scientist and esophageal surgeon and coauthor of the study said, “This is a landmark study into the genetic basis of why and how some people with Barrett's esophagus get esophageal cancer and others do not. It is still early, but we very much hope that this information will lead to a game-changer for a cancer with one of the worst outcomes.” The study was published on June 22, 2014, in the journal Nature Genetics.

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University of Cambridge
University of Southampton
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