Peter Van Loo diagram.

Peter Van Loo : Molecular archaeology of cancer: inferring timelines of cancer development and evolution

Introduction

The cancer genome contains an archaeological record of its past.

The cancer genome contains an archaeological record of its past and we previously pioneered methods to disentangle a cancer's life history from sequencing data.

We anticipate that a large-scale pan-cancer approach to obtain detailed evolutionary histories of tumours would give profound insights into carcinogenesis and cancer evolution.

Molecular archaeology of cancer: an example.

Figure 1: Molecular archaeology of cancer: an example. From the picture on the right, one can infer that the purple mutations happened first, then the blue chromosome duplicated, and then the yellow mutations occurred. In addition, from the relative numbers of yellow and purple mutations, one can infer when in the tumours lifetime the blue chromosome duplicated.

We can construct life histories of thousands of tumours from their genome sequences, using both driver and passenger mutations.

By obtaining detailed timelines of many cancers' evolutionary histories that include driver mutations, copy number changes, rearrangements and mutational processes, we will identify the initiating events of cancer development and the events that are selected for later in a cancer's lifetime, including those that drive late clonal expansions and that may play a role in tumour malignancy.

In addition, these analyses will allow blueprints of the subclonal architecture across cancer types in unprecedented detail and on an unprecedented number of cases, allowing a glimpse into a tumour's future.

Complementary to this, we are performing smaller-scale collaborative studies of tumour bulk sequencing, in combination with single-cell and multi-sample sequencing of primary tumours, metastases and circulating and disseminated tumour cells, aiming to gain insight into tumour evolution and metastasis.