An epigenetic algorithm traces the origin of cancer and predicts its progression

A study, published in Nature, has analyzed the evolution of lymphomas and leukemias in samples from 2.000 patients and has discovered that DNA methylation marks act as a 'black box' capable of revealing the origin of tumors and anticipating their clinical behavior.

A scientific team led by Clínic-IDIBAPS (Barcelona) and the Institute of Cancer Research in London has developed an innovative method based on DNA methylation to decipher the origin and evolution of cancer, which also allows for predicting its clinical course. The study, published in the journal Nature, analyzes the evolution of tumors in 2,000 patients with leukemia and lymphoma.

Cancer doesn't begin at the moment of diagnosis, but often develops silently over years. Similar to an airplane's "black box," which records flight data such as origin, direction, and speed, researchers have discovered that the evolutionary trajectory of cancer is encoded in the epigenome. Specifically, it is found in a special type of epigenetic mark known as fluctuating methylation.

Until now, methylation was understood mainly as a switch that turns genes on or offHowever, the new work shows that it serves an additional function: the original cell that gave rise to the tumor leaves a unique methylation signature. This fingerprint not only reveals the identity of the tumor cells, but also changes as the tumor grows and diversifies.

mathematical models

Using advanced mathematical models, the team was able to decipher these methylation patterns and reconstruct both the origin and evolution of the tumor with unprecedented precision, which also allows them to predict its future development.

The algorithm, called EVOFLUx, was applied to 2,000 samples from patients with different types of leukemia and lymphoma. “We reanalyzed old epigenetic data from a completely new perspective,” he comments. Calum Gabbutt, from the Institute of Cancer Research in London. “What we once considered background noise now reveals the evolutionary history of cancer,” he adds. Martí Durán-Ferrer, from IDIBAPS.

“This new tool allows us Read the past history of the cancer and know when the tumor originated, how fast it has grown, and whether it has created cellular diversity. This is not only important for better understanding cancer biology, but also has clinical applications," he emphasizes. Iñaki Martín-Subero, ICREA researcher at IDIBAPS and coordinator of the study.

Anticipate clinical progression

The study was based on the hypothesis that understanding a cancer's history allows us to predict its clinical future. To this end, samples from patients with lymphoid cancers were analyzed, including pediatric leukemias such as acute lymphoblastic leukemia and adult diseases such as chronic lymphocytic leukemia.

With access to the anonymized medical recordsThe researchers correlated the tumor's past evolution with its aggressiveness. "Cancers change over time, which complicates their treatment," he explains. Trevor Graham, director of the London Cancer and Evolution Centre. “We discovered that the initial growth of cancer determines how it will evolve in the future, allowing us to predict progression in each patient. This is a major step forward in personalized disease management.”

Martín-Subero adds: “In the case of the chronic lymphocytic leukemia, a type of cancer that doesn't always require immediate treatment, with this new test we can predict when the disease will need treatment years in advance." He adds: "Although in this study we analyzed leukemias and lymphomas, we believe this methodology could be applied to all types of cancer."

Reference:

Calum Gabbutt et al. “Fluctuating DNA methylation tracks cancer evolution at clinical scale.” Nature, 2025

Source: Sinc Agency