Study sheds light on epigenetic changes in cancer progression

BARCELONA: Every cell produces its own proteins by utilising the genetic information contained in its genes. Mutations are changes in this information that can disrupt the function of the affected proteins. This is known as cancer genetics in oncology.

However, in recent decades, a new area has emerged: cancer epigenetics. Epigenetic changes do not alter the information, but rather alter the cell's capacity to read certain of its own genes and make the corresponding proteins.

There is a huge epigenetic programme that controls the general functioning of the cell and, when disrupted, can put it on the path to malignant transformation.

An international team of researchers has started to unlocked this long-awaited milestone. In a tour de force, they analysed 1.7 million cells from 225 samples from primary and metastatic origin, from 205 patients of 11 different cancer types. For each cell, the team obtained the full transcriptome, exome and epigenome.

This covers virtually all gene mutations, gene accessibility and its consequences. Using vast computational power, they could deduce the whole functional status of each analysed cell and link it to its particular cancer type.

The results of the work, published at the prestigious scientific journal Nature, demonstrate that many regions in the DNA are differentially activated or inactivated in a cancer-specific manner, creating a signature for each tumour.

These differences are relevant for cancer progression and many correspond to already identified hallmarks of cancer, the steps a cell must undergo to become malignant. Dr. Eduard Porta, group leader at the Josep Carreras Leukaemia Research Institute (IJC-CERCA), is part of the team and contributed with his experience in the analysis of large amounts of biological data.

Epigenetic changes at the DNA level stand out as an underlying cause of cancer, according to the new publication. Particularly, the accessibility of enhancer regions, a kind of master regulator acting upon many genes at once.

Taken together, the results converges into a short list of genes that can be used as markers for good or poor prognosis, valuable information for the clinical management of patients.

The analysis has also identified the cellular pathways of these important genes, making it possible to track their distant interactions.

Sometimes, the affected genes are so fundamental that is impossible to drug them directly without side effects but, knowing the full pathway, researchers may develop strategies to target the weakest link in the chain, maximising the therapeutic benefits while minimising undesirable effects.