A research team from IDIBAPS-Hospital Clínic and the University of Barcelona has led an international study to develop an epigenetic clock that can trace how much the cancer cells have multiplied in the past. Thanks to this clock, they can predict the future growth of the tumour and clinical evolution of patients, so they could define treatment strategies according to the biological risk of the tumour.
The study, published in the journal Nature Cancer, has been coordinated by Iñaki Martín-Subero, ICREA research professor at IDIBAPS and lecturer at the Department of Basic Clinical Practice of the UB, and counted on the participation of thirty-two researchers from sixteen institutions and six different countries.
Recently, scientific studies revealed that epigenetics is not only the science that studies genes that are silenced or activated, but it also holds a function of cell memory. According to Martín-Subero, “we could say that the genome, which is the encyclopaedia of the current life in each cell, is formed by two types of books: the open one, with active genes, and the closed one, with genes that are silenced”. Researchers saw that the epigenetic changes that take place in the closed book of the genome store a hidden memory of the past cell growth.
In the framework of the published study in Nature Cancer, the researchers studied the epigenetic alterations in more than 2,000 patients with different types of leukaemias and lymphomas, and saw that each time the cells reproduce, these write small marks in the closed book of the genome. According to Martí Duran-Ferrer, first signatory of the study, since epigenetic changes related to cell growth are accumulative, they could develop “an epigenetic clock that reflects how cells multiplied in the past”. “We observed that, if this clock advances in the past, it will do so in the future, and this is directly associated with the presence of certain genetic mutations and the clinical aggressiveness of the patients”, adds the expert.
To date, the epigenetic changes in the closed book of the genome were regarded as silent companions of the tumor transformation process, without clinical involvements. Martín Subero notes, however, that this study reveals that “the accumulated epigenetic changes in the genome of the tumors are important, since they predict the future clinical behaviour of the patients. Cancer cells write a great part of their history in this closed book”.
Researchers warn that there is still a lot to do before this epigenetic clock reaches the clinics. However, the strength of the data suggests the molecular clock could help define treatment strategies that better fit the tumor biological risk.
The director of Research at the Hospital Clínic and IDIBAPS, Elías Campo, professor of Pathological Anatomy at the UB and co-author of the article, concludes that “this study shows a new view on how to anticipate the clinical behaviour of the patients with lymphoid cancer and it has a great potential to become an important variable for the clinical management of cancer in the age of customized medicine”.
Duran-Ferrer, M.; Clot, G.; Nadeu, F.; Campo, E.; Martín-Subero, I. et al. “The proliferative history shapes the DNA methylome of B-cell tumors and predicts clinical outcome”. Nature Cancer, November, 2020. Doi: https://doi.org/10.1038/s43018-020-00131-2