By: Alison Ollikainen and Tatiana Cajuso
The Tumor Genomics Research Group at the University of Helsinki serves as a link connecting clinical and epidemiological areas to the computational and experimental activities within the Center of Excellence in Tumor Genetics. To this end the group provides expertise particularly in the complex world of medical genetics as well as in clinical medicine and is in close collaboration with clinicians nationally as well as internationally. Here we meet Tatiana Cajuso, a PhD student from the group, who explains her work in further understanding the role of retrotransposon insertions, or “jumping genes”, in cancer by utilizing whole genome sequencing data.
Can you introduce yourself?
My name is Tatiana Cajuso, a PhD student in the Tumor Genomics Group at the University of Helsinki and I am, hopefully soon ;), completing my PhD work.
On a broad level, what did you study during your PhD?
From the beginning I took part in the colorectal cancer (CRC) project where, at that moment, we had sequenced the whole genomes of both the tumors and normal tissue of almost 100 colorectal cancer patients.
What can we learn from whole genome data?
Whole genome data comes from sequencing the DNA of pretty much the entire human genome instead of only a specific gene or a specific group of sequences. By looking at the genome as a whole, we can, for example, comprehensively characterize rearrangements involving different regions of the genome, such as retrotransposons.
What are retrotransposons?
Retrotransposons are DNA sequences that can copy and paste themselves into new locations of the genome, hence the name jumping genes. Since every time they jump, they insert DNA into a new location, they can be a source of mutagenesis. Jumping genes can be found in the genome of almost every single living organism, however, in healthy tissues, they remain under strict control.
I had never heard of retrotransposons until I met you and read your work. How did you first come across retrotransposons?
Since we had the whole genome sequence from many CRC patients, we observed that there was a recurrent change always arising from the same region of a gene which was going to other locations. This recurrent change had been previously interpreted as a translocation that was likely to inactivate the gene in question. Translocations are rearrangements that involve the breakage of a DNA sequence and its reattachment to another location. However, when we looked closely into our data, we interpreted these changes as retrotranspositions rather than translocations. The distinction between translocation and retrotransposition is important. From our data, we did not predict the inactivation of the gene where the retrotransposon was residing, since retrotransposons copy themselves and only the copy is mobilized.
Are these “jumping genes” responsible for causing cancer?
I would rather say that they can contribute to cancer, although it should be further explored to which extent they can do so. The effect of jumping gene insertions mostly relies on where they go and what effect they may cause at the target site. It is also important to realize that jumping genes comprise almost half of the human genome.
Oh wow, that’s a lot…
…Yeah it’s a lot, but most of those are just “fossils”, remnants of ancient retrotranspositions which are no longer jumping around. Only a small subset of them remain potentially active today. However, since it is not “safe” to have stuff jumping around in a healthy genome, the potentially active ones are normally repressed.
Is there more to learn about jumping genes, and their potential role in tumor development?
A lot in my opinion 🙂
During the past decade, there have been a bunch of studies using whole genome sequencing to understand the impact of jumping genes in cancer. From these studies, we have learnt many things. For example, we know that jumping genes are very active in different cancers and they can jump into genes known to affect cancer development. Also, we have started to observe links between the number of insertions+ and molecular and clinical characteristics, such as cancer prognosis. However, jumping genes remain difficult to detect and their study still presents many challenges. With further development of molecular techniques, we will likely gain a better understanding on how and to which extent jumping genes may impact cancer.
Is there a positive side to jumping genes? Any functional reason why they occur? If they can be detrimental, why have they not been selected against?
That is a very good question. We do know that jumping genes can contribute to genetic variation but also uncontrolled “jumping” can lead to instability in cancer genomes. Therefore, jumping genes may have survived in our genomes and the genomes of other species, because their impact in evolution has not been strikingly detrimental. It is possible that the lack of negative selection has contributed to the evolution of jumping genes.
Aren’t you now reading the biography of a woman who first put forward evidence of mobile genetic elements?
Yes :), jumping genes or mobile elements were discovered by Barbara McClintock and reported in the paper she published in 1956. Although her findings did not sink into the scientific community at that time, the Nobel Prize in Physiology or Medicine in 1983 was awarded to her for her discovery of mobile genetic elements.
Thanks very much Tatiana for talking to me and congratulations on finishing your thesis and I look forward to your doctoral defense!
Thank you! Let’s celebrate it soon! 😉