Tissue structure delays cancer development, reveals computer model

Cancer growth normally follows a lengthy period of development. Over the course of time, genetic mutations often accumulate in cells, leading first to pre-cancerous conditions and ultimately to tumour growth.

Using a mathematical model, scientists at the Max Planck Institute for Dynamics and Self-Organization in Göttingen, University of Pennsylvania and University of California San Francisco, have now shown that spatial tissue structure, such as that found in the colon, slows down the accumulation of genetic mutations, thereby delaying the onset of cancer. Their model could help in the assessment of tissue biopsies and improve predictions of the progression of certain cancer types.

Many types of cancer develop unnoticed in the body over a long number of years before the disease erupts. The point of departure is provided by specific genetic mutations including point mutations, copy number alterations, loss of heterozygosity, and other structural rearrangements, that gradually accumulate in the cells, leading to the formation of pre-cancerous lesions.

If a certain number of mutations is reached in individual cells, the cells begin to proliferate unchecked. For some cancer types, the accumulation process can take up to 20 years. However, not everyone with pre-cancerous tissue will actually develop cancer; the formation of abnormal cells often has no medical consequences. To date, it is still unclear why tumours develop in some cases and not in others.

Using mathematical modelling, a research group headed by Erik Martens and Oskar Hallatschek of the Max Planck Institute for Dynamics and Self-Organisation in Göttingen have studied how genetic mutations spread, the speed of the mutation accumulation process, and the impact of this process on the progression of pre-cancerous conditions.

They have shown that the destiny of oncogenic or cancer-causing mutations depends in part on where they occur and how much competition they are exposed to from other, similar mutations. In an environment without any spatial structure, for example in the blood, genetic mutations can propagate and accumulate relatively fast. In tissue with clear spatial structure, such as that of the colon, however, it takes longer for cells to accumulate the number of mutations required for tumour formation.