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Triggers and drivers of latent epigenomic structure in colorectal cancer

Research Leader:

Miguel A. Peinado

Institution:

Institut de Recerca Germans Trias i Pujol (IGTP)

Collaborators: 

Berta Martin, Núria Seguí, Júlia Matas, Mar Muñoz

Project description

Cancer cell functional reprogramming involves gene expression dysregulation driven by genetic and epigenetic changes. In recent years, fundamental studies have set the reference maps of the human genome and epigenome in normal and cancer cells and have provided important clues about the drivers and the mechanisms behind many tumor types, and more importantly, about the uniqueness of each cancer.

Colorectal cancer is a complex and heterogeneous disease with a significant health impact worldwide. The early application of most advanced technologies to colorectal cancer research, diagnosis and treatment has made this disease a paradigm in molecular medicine.

In previous studies we found consistent patterns of compartmentalization in both normal and colorectal tumor tissues. We also identified large transchromosomal modules with unique regulatory signatures and that coalesced into a structured network. Co-methylating modules denoted functional aggregates, pointing out potential sources of epigenetic and phenotypic variability. These data suggest that DNA methylation dynamics architecture embodies interpretable information that can be used as a proxy of both the drivers and the phenotypes of malignant transformation.

Here, we hypothesize that by decomposing the latent structure of DNA co-methylation network it is possible to pinpoint potential triggers and drivers of cancer cell transformation. The general objective of this project is to decipher the contribution of specific genetic and epigenetic alterations to orchestrate the functional remodeling of cancer cell's genome. 

Contact person: mpeinado@igtp.cat

Web link: http://www.germanstrias.org