Ewing's sarcoma: the epigenetics route
Olivier Delattre, directeur de l'unité Génétique et biologie des cancers - Institut Curie / Inserm U830.
Ewing sarcomas are a rare form of bone cancer affecting children and young adults. Institut Curie is a leading center in both diagnosing these illnesses (thanks to its scientific expertise) and providing treatment (thanks to its hospitalization unit for adolescents and young adults).
The genetic anomalies responsible for these cancers are relatively straightforward. Translocation shifts a fragment of DNA to an entirely different location in the genome, or in a different gene or chromosome. This genetic abnormality results in chimeric protein, itself an abnormality, that latches on to specific DNA sequences, as they are repetitive GGAA-motifs. The number of repeated sequences varies sharply from one individual to the next, and in particular from one patient to another. By latching on to these sequences, the chimeric protein alters their epigenetic context depending on the number of repetitive units involved. This means a relatively simple genetic alteration results in epigenetic modifications that range widely between patients. “We’re trying to understand how these epigenetic modifications might impact on metastases, cancer resistance to immunotherapy and the risk of relapse. It may allow us to adapt treatments to each patient. We know that this illness is much more frequent in European populations compared to African populations. There have already been studies into these variabilities, but links with clinical aspects remain to be demonstrated. And because this form of cancer is rare, it’s difficult to study. Hospitals need to keep tumor samples for research, they need to take part in international collaborative projects so that we improve the statistical accuracy of our observations. They need to use specific DNA sequencing techniques to study long DNA fragments,” explains Olivier Delattre. That’s the message he’ll be sharing with colleagues on 22 October at the European Society for Medical Oncology‘s annual congress in Munich.