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Johns Hopkins Pediatric

Trouble on LINE-1

Stephen Meltzer, MD

Stephen Meltzer says LINE-1 is an early marker for premalignancy and cancer in the esophagus.

It sounds like the plot of a cyber thriller: Programming code copies and then wedges itself into other parts of the program.

But it’s not a movie, and we’re talking about genetic code, not computer code.

The retrotransposon long interspersed element-1, or LINE-1, is a chunk of code from the human genome that researchers believe has been copying itself and jumping around the human genome for hundreds of thousands of years. LINE-1, while not part of the human genome referencing sequence, is very common. It can be harmless, or it can cause mutations. And as Johns Hopkins researcher Stephen Meltzer and his collaborator, Haig Kazazian, have found, the jumping process occurs in cancer and precancerous parts of the body.

Meltzer and Kazazian discovered that the LINE-1 sequence occurs quite frequently in the premalignant tissue known as Barrett’s esophagus.

“Retransposition happens very early, even in normal esophageal tissue,” Meltzer explains. “It appears to occur pretty much at random. Then, some of these events become amplified in Barrett’s esophagus.”

Meltzer cautions against assigning cause-and-effect status to LINE-1, though.

“We don’t know if they cause, or are merely passengers in, malignant progression,” he states. “We haven’t yet proven that they’re carcinogenic.”

He does believe, though, that LINE-1 is an early marker for premalignancy and cancer in the esophagus.

“Where there’s a genetically unstable environment, like the one created by acid reflux, it’s easier for these genes to jump,” says Meltzer. “The damage and inflammation induced by acid are associated with LINE-1 retrotransposition. So, in a sense, this jumping is itself a good biomarker for a bad environment.”

Meltzer suspects that this new biomarker might help detect the danger of cancer sooner than does the current histologic marker, Barrett’s esophagus.

“We knew that many types of molecular abnormalities could occur, but this is a new kind of alteration we didn’t know could happen occur in Barrett’s due to GERD,” Meltzer explains. “So, this represents a new potential mechanism. Whether it causes cancer is open to question. But we do know it occurs during the carcinogenic process and shows promise as an early detection biomarker.”

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