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Study finds molecular 'signature' for rapidly increasing form of esophageal cancer
Date:3/24/2013

hagus change to resemble cells in the intestine. Patients with Barrett's esophagus often go on to develop EAC.

Researchers don't know why EAC rates are increasing, but they speculate that it may be due to a rise in obesity, particularly in men: A heavier abdomen puts increased pressure on the stomach, causing acid to back up into the esophagus.

In the new study, researchers "sequenced" specific sections of DNA in cells from 149 EAC tissue samples, reading the individual letters of the genetic code within those areas. They focused on the one percent of the genome that holds the codes for making cell proteins. They also sequenced the entire genome all the DNA within the cell nucleus of cells from 15 of these EAC samples. Prior to this study, the largest sequencing study of EAC involved only a dozen tumor samples.

"We discovered a pattern of DNA changes that had not been seen before in any other cancer type," Getz remarked. The pattern involved a subtle swap in one of the four "nucleobases" that form the rungs of the DNA double helix, often designated by the letters C, T, G, and A. The investigators found that in many places where an A nucleobase was followed by another A nucleobase, the second "A" was replaced by a "C," a process known as transversion.

"We found this type of transversion throughout the genomes of the EAC cells we analyzed," Bass stated. "Overall, about one-third of all the mutations we discovered within these cells involved this type of transversion. In some tumor samples, these transversions accounted for nearly half of all mutations," Getz added.

Although A-to-C changes are not commonly observed in cancer, there is some evidence that oxidative damage can produce these changes. (Oxidative damage occurs when cells cannot neutralize the potentially harmful products of oxygen's reactions with other molecules.) "Gastric reflux can produce this type of damage, suggesting that reflux may underlie this pattern of mutations," Bass
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Contact: Anne Doerr
anne_doerr@dfci.harvard.edu
617-632-5665
Dana-Farber Cancer Institute
Source:Eurekalert

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