Bioinformatics and Evolutionary Genomics of Cancer

Research project

The scientific activity of our lab focuses on the analysis of cancer genome. Currently, we study cancer-specific traits involving both coding and non-coding regions of the human genome and pursue three main lines of investigation:

Quantification of genome instability of tumour cells using next-generation sequencing (NGS)
We apply NGS to estimate cancer-associated genomic instability, that is the tendency of cancer cells to accumulate a number of mutations higher than normal cells. The identification of genomic instability with high sensitivity is of paramount importance because it can be used to detect the early stages of tumour initiation.

Evolution and systems biology of cancer genes.
Genes implicated in cancer development are highly heterogeneous from a functional point of view. Yet, they all interfere with key cellular pathways involved in cell proliferation and death. This suggests the presence of common properties not directly dependent on the molecular function of single genes. We analyzed ~600 genes mutated in cancer not focusing on each gene separately, but seeking for the presence of ‘systems-level’ properties. We have found that cancer genes tend to avoid duplications and code for central hubs of the protein-protein interaction network. We plan to use the detected properties to identify novel portions of the human network putatively involved in cancer.

In-depth evolutionary analysis of cancer gene families.
We aim at characterizing the evolution of cancer-related genes to gain information on their functional roles. In the past years, we traced the metazoan origin of the PRDM genes, a family of transcriptional regulators involved in human tumorigenesis. We detected the expansion of this family in vertebrates and further specific duplication in primates. We experimentally showed that fast-evolving paralogs are poorly expressed and acquire tissue-specificity. Our findings allowed a novel interpretation of the role of PRDMs during cancerogenesis.