Epigenetic heterogeneity in cancer

Paola Scaffidi : Epigenetic determinants of functional diversity within tumours

Introduction

In many cancers, only small subsets of cells are endowed with unlimited proliferative potential and are responsible for maintaining tumour growth, whereas the rest of the cells display a more differentiated phenotype and only have limited ability to proliferate.

The molecular basis underlying the functional differences among subpopulations of tumour cells are at present unclear.

Since subsets of cancer cells lose tumorigenic potential through a differentiation process, epigenetic mechanisms are likely to play a critical role in defining the malignant phenotype of a cancer cell within a growing tumour.

We are employing genome-wide mapping approaches to characterise the chromatin landscape of self-renewing cancer cells and identify epigenetic features which distinguish them from the rest of the tumour. By combining these studies with in vivo gain- and loss-of function experiments and analysis of publicly available datasets from cancer patients, we aim to identify epigenetic features which are critical for tumour maintenance and can be modulated for therapeutic purposes.