Epigenetic heterogeneity in cancer

Introduction

The Cancer Epigenetics Laboratory studies cellular mechanisms important for cancer development, with a particular focus on processes affecting how cells use their DNA.

Phenotypic intratumour heterogeneity.

Figure 1: Phenotypic intratumour heterogeneity. Immunofluorescence microscopy of a breast cancer section showing highly heterogeneous patterns of methylated histone H3 (green) and histone H1.0 (red).

Although every cell in the body contains the same DNA, different cell types utilize distinct groups of genes to perform their specific function. Processes responsible for defining cellular identity, known as epigenetic mechanisms, modulate the DNA’s tri-dimensional structure to switch certain genes on and others off, and establish cell type-specific cellular programs.

Every normal cell knows which sets of genes need to be activated to ensure proper cell function, and is able to transfer this knowledge to its daughter cells. However, in cancer cells lose their memory and begin to use genes inappropriately, leading to altered cell behaviour, uncontrolled proliferation and invasion of normal tissues.

We are interested in understanding how epigenetic mechanisms cooperate with genetic alterations and cell-to-cell communication to promote cancer development. How do cells acquire a new identity in the early stages of the disease? How do they diversify from one another while the tumour grows, leading to a heterogeneous collection of cells with different properties? How can we interfere with these processes to treat cancer more effectively? We address these questions using a wide range of approaches that combine cellular and molecular techniques, mouse genetics, and the analysis of clinical samples.