Understanding the intricate interplay between genetics and cancer progression has long captivated the scientific community. While genetic mutations have been the main focal point in oncology, recent strides have illuminated the profound influence of epigenetic modifications in the development of cancer.
In a recent study published in the journal Nature, Dr. Eduard Porta from the Josep Carreras Leukaemia Research Institute and his team have shed light on the pivotal role that epigenetics plays in steering cells on their journey from healthy to metastatic cancer.
Unlike genetic mutations, epigenetic modifications don’t alter the DNA sequence itself; instead, they transiently modify a cell’s ability to interpret specific genes, influencing which proteins are produced. Primary mechanisms underlying epigenetic changes include DNA methylation, histone modifications, and chromatin remodeling.
Several studies have focused on understanding the link between epigenetic modifications and cancer development. These studies aim not only to pinpoint markers useful in diagnosing and predicting cancer outcomes but also to explore therapies that capitalize on the reversible nature of these epigenetic changes.
In this study, the researchers aimed to investigate the relationship between gene transcription and chromatin accessibility, which denotes the extent to which chromatin is open and accessible for gene regulation and subsequent transcription. They used advanced techniques such as ATAC-seq (assay for transposase-accessible chromatin sequencing) and snRNA-seq (single-nucleus RNA sequencing).
Their analysis included 1.7 million cells from 225 samples representing various cancer types and provided a comprehensive view of the cells’ transcriptomes, exomes, and epigenomes. This deep dive into cellular genetic instructions and their accessibility offered insights into the functional status of each cell, linking it to specific cancer types.
The study’s findings uncovered that specific regions of DNA undergo differential activation or inactivation in a cancer-specific manner, essentially creating a unique fingerprint for each tumor. These alterations correspond to well-known hallmarks of cancer, the distinct steps cells take as they transition into malignancy. Dr. Eduard Porta’s expertise in managing extensive biological data was instrumental in this study.
At the heart of these epigenetic alterations lay the accessibility of enhancer regions—masters orchestrating the activity of multiple genes simultaneously. Collectively, these results pinpointed a select group of genes that could serve as markers for predicting patient prognosis, offering valuable insights for clinical decision-making.
Moreover, the analysis illuminated the intricate pathways associated with these crucial genes, opening avenues to understanding their interactions within cells. While some of these genes may be too fundamental to be directly targeted with drugs without causing side effects, understanding their complete pathway enables researchers to identify potential vulnerabilities. This strategic approach could maximize therapeutic benefits while minimizing adverse effects, which is an essential step toward more effective cancer treatments.
This study not only highlights the critical role of epigenetic changes in cancer but also paves the way for personalized and targeted therapeutic strategies, offering hope in the ongoing battle against this complex disease.
Source: Nadezhda V, et al. Epigenetic regulation during cancer transitions across 11 tumour types. Nature, November 1, 2023.
Reference: Epigenetic changes are paramount in cancer progression. Josep Carreras Leukaemia Research Institute. November 6, 2023.