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Cytosponge Helps Spot Early Signs of Esophageal Cancer

By LabMedica International staff writers
Posted on 05 Aug 2015
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Image: The Cytosponge cell sampling device shown contained in its gelatin sheath and when expanded (Photo courtesy of MRC Cancer Unit).
Image: The Cytosponge cell sampling device shown contained in its gelatin sheath and when expanded (Photo courtesy of MRC Cancer Unit).
A “pill on a string” has been developed that could help doctors detect esophageal cancer, also known as cancer of the gullet, at an early stage, helping them overcome the problem of wide variation between biopsies.

The “Cytosponge” sits within a pill which, when swallowed, dissolves to reveal a sponge that scrapes off cells when withdrawn up the gullet and allows doctors to collect cells from all along the gullet, whereas standard biopsies take individual point samples.

Scientists at the University of Cambridge (UK) and their colleagues at different institutions, carried out whole genome sequencing to analyze paired Barrett's esophagus and esophageal cancer samples taken at one point in time from 23 patients, as well as 73 samples taken over a three-year period from one patient with Barrett's esophagus.

Whole-genome sequencing was performed on the HiSeq 2000 instrument (Illumina, San Diego, CA, USA). The teams found patterns of mutations in the genome that provided a “fingerprint” of the causes of the cancer. Similar work has been done previously in lung cancer, where it was shown that cigarettes leave fingerprints in an individual's DNA. The Cambridge team found fingerprints which they believe are likely to be due to the damage caused to the lining of the esophagus by stomach acid splashing onto its walls; the same fingerprints could be seen in both Barrett's esophagus and esophageal cancer, suggest that these changes occur very early on the process.

Even in areas of Barrett's esophagus without cancer, they found a large number of mutations in their tissue, on average 12,000 per person compared to an average of 18,000 mutations within the cancer. Many of these are likely to have been “bystanders,” genetic mutations that occurred along the way but that were not actually implicated in cancer. They also found that there appeared to be a tipping point, where a patient would go from having lots of individual mutations, but no cancer, to a situation where large pieces of genetic information were being transferred not just between genes but between chromosomes.

The authors concluded that from a clinical perspective, the histopathological assessment of dysplasia appears to be a poor reflection of the molecular disarray within the Barrett's epithelium, and the molecular Cytosponge technique overcomes sampling bias and has the capacity to reflect the entire clonal architecture.

Rebecca Fitzgerald, MD, a professor who developed the Cytosponge, said, “The trouble with Barrett's esophagus is that it looks bland and might span over 10 cm. We created a map of mutations in a patient with the condition and found that within this stretch, there is a great deal of variation amongst cells. Some might carry an important mutation, but many will not. If you're taking a biopsy, this relies on your hitting the right spot. Using the Cytosponge appears to remove some of this game of chance.” The study was published on July 20, 2015, in the journal Nature Genetics.

Related Links:

University of Cambridge 
Illumina 


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