Double helix showing coplanar alignment of standard base pairs.WIKIMEDIA COMMONS, MUSHII

Within the human genome, small DNA elements called retrotransposons have the potential to wreak mutational havoc by copying themselves and reinserting into the genome at multiple locations. Normal adult cells have suppressive mechanisms to stop these elements from jumping about, but according to a report published today (June 28) in Science, those mechanisms can break down in certain cancers. The findings suggest that, in some cases, jumping genes might even cause cancer or contribute to its progression

“The paper is very important,” said Keith Slotkin a molecular geneticist at Ohio State University in Columbus, who did not participate in the study. “There has long been a weak association between cancer and transposable element activity, but this paper now categorically shows that transposable element activation is a source of new mutations in cancer cells.”

Retrotransposons are common in eukaryotic...

“Most are molecular fossils—dead pieces of DNA,” explained John Moran a human geneticist at the University of Michigan Medical School in Ann Arbor, who did not participate in the research. That is, they have accumulated so many mutations over the course of evolution that they are now merely inactive remnants. “But,” he said, “Some are actively mobilizing.

Normal adult cells keep these mobile elements under control using a number of mechanisms including epigenetic suppression to prevent their expression, and mRNA degradation to catch those that are transcribed, explained Slotkin.

But a handful of reports documenting retrotransposon insertions in tumor cells suggest that these suppressive mechanisms might go awry in some cancers. Peter Park of Harvard Medical School in Boston wanted to know just how common such cancer-related retrotransposon activation was. “Whole genome sequencing technologies have now allowed us to look at this in a very comprehensive way,” he said.

There was one complication, however: traditional sequencing software programs are designed to specifically omit repeated DNA elements like transposons, explained co-author Peter Kharchenko, also of Harvard Medical School. So Kharchenko and Park designed a new program called TEA, transposable element analyzer.

The team used TEA to compare the whole genome sequence data of tumors and normal tissues taken from 43 cancer patients. TEA searched the genomic sequence fragments for ones containing both repeat elements and unique sequence data to determine the exact position of transposable elements in the genomes, and it found nearly 200 novel insertions in the tumor genomes. Sixty-four of these occurred in genes, many of which are commonly mutated in cancer. The insertions often affected expression of those genes, suggesting a causative or contributing role in the cancer.

Interestingly, while insertions were relatively common in cancers of epithelial origin, such as colorectal and ovarian, not one was detected in tumors of the blood or brain. “Understanding why there may be cell-type-specific differences that provide more permissive environments for retrotransposition would be very interesting to follow up,” said Moran.

“Retrotransposition is clearly not the only mechanism contributing to mutagenesis and cancers,” said Kharchenko “but it is an option that hasn’t been considered previously. ”

The team now plans to extend their analysis, and apply the TEA software to as many cancer genomes as possible.  “If it is prevalent enough,” said Kharchenko, and if it does appear to contribute to cancer pathology, “then you can start thinking about ways to target it.”  A lot of these elements behave like retroviruses, he added, so research on suppressing retroviruses might be equally useful for designing therapies to keep retrotransposons in place.


E. Lee et al., “Landscape of somatic retrotransposition in human cancers,” Science, doi: 10.1126/science.1222077, 2012.

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