Sometimes research has lucky stories behind it that should be told. We usually think of a Master’s thesis as another task to earn the degree certificate, but once in a blue moon it ends up being the milestone for future scientific discoveries.

Nothing to lose

Alicia BruzosIn 2015, I was studying a master’s degree in bioinformatics at Universitat Autònoma de Barcelona when some scientists that I admired told me about Jose Tubío, a researcher working in Cambridge that was moving back to Spain. I had nothing to lose so I wrote him an email. After several meetings, he proposed I make a catalogue of retrotransposons that become active in the cancer genome. Retrotransposons, also known as jumping-genes due to their ability to move in the genome, represent an important part of our genetic material. For a long time, they have been considered “junk DNA” because of their repetitive nature and apparent absence of a clear function in the genome. This misconception led many scientists not to dig into the potential role of these regions in cancer.

However, my master thesis supervisor has been developing the algorithms to study the activity of these jumping-genes in the cancer genome since 2010. The Pan-Cancer Analysis of Whole Genomes (PCAWG) project gave us the opportunity to see the activity of these jumping-genes in over 2500 cancer patients.

The findings

Alicia Retrotransposons
The catalogue of active retrotransposons
on cancer genomes

Retrotransposons are mobilized in the cancer genome more frequently than in non-tumor cells. Using bioinformatic algorithms we got the exact location of these jumping-genes in all of the patients. Thus, we produced a chromosome map with the ones that were active – those that were jumping in cancer genomes. Interestingly, 114 retrotransposons were jumping with 16 of these elements showing hot activity because 67% of the “jumps” are produced by them. In other words, they cause more than three quarters of all mutations caused by retrotransposons in a tumor.

If we pay attention to their activity, these jumping-genes behave like volcano eruptions. Some of them – strombolian retrotranspositions – are frequently active in cancer but are rarely mobilized. This is like Mount Stromboli, which has been erupting continuously for centuries. Others such as plinian retrotranspositions mobilize less frequently. However, when they do it is very similarly to the eruption of Mount Vesuvius that buried the Roman town of Pompeii.

Alicia Bruzos
Activity pattern of active retrotransposons on cancer genomes

Getting published in Nature

Cataloguing the ‘jumps’ of retrotransposons in thousands of cancer patients was not only my master thesis. It is also one of the pieces of this story that has been recently published in one of the top journals in science – Nature – in an article describing the main outcomes of the PCAWG project. I never knew it would end up in Nature when I was doing the catalogue. It was actually three years after my master thesis submission when we were accepted. Even then, we had to wait until this year to see the article in paper because the journal was preparing a special issue grouping works done in cancer genomics.

Alicia Bruzos
Jose Tubío (center) supervised the master thesis of Alicia L. Bruzos (second from right) in the framework of the Pan-cancer international project.

And that is the story of a master thesis cataloguing jumping genes that ended up being published in Nature. It was a dream of the little scientist inside me. Nowadays, I continue working in cancer genomics trying to understand the process of metastasis. In other words, instead of looking at jumping genes, I’m looking at jumping cells, but that’s a story for another day.

Want to know more?

Take a look at the Nature paper where you can read more details: Campbell, P.J., Getz, G., Korbel, J.O. et al. Pan-cancer analysis of whole genomes. Nature 578, 82–93 (2020).