Modeling the interplay between processes that induce cancer-causing mutations

2021

Challenge

The DNA of cancer cells is exposed to various mutation-generating processes, causing the cells to accumulate many mutations. Many of these ‘mutagenic’ processes leave characteristic imprints on the genomes of those cells, called mutational signatures. These signatures can be used to identify the processes that contributed to the mutations in a cancer’s DNA. Therefore, differentiating the various types of mutation-inducing processes is a difficult and important challenge in studies of cancer genomes.

Advance

IRP investigators led by Teresa Przytycka, Ph.D., developed RepairSig, a computational method that identifies mutational signatures and models mutagenic processes. The method distinguishes between two types of mutagenic processes, called ‘primary’ and ‘secondary’ processes. Primary processes, which include environmental factors such as UV light and smoking cigarettes, additively affect genomes independently from each other, while secondary processes are related to DNA repair pathway deficiencies and act on the outcomes of primary processes.

Impact

This study provides an important step towards a rigorous modeling of the complex interactions between mutagenic processes and has the potential to becoming a stepping stone for further studies. Knowledge of primary processes related to the environment can be valuable for cancer prevention. In contrast, understanding the nature of secondary processes, such as deficiency in DNA repair pathways, might guide cancer treatment by leading to the creation of drugs that selectively kill cells with deficiencies in particular DNA repair pathways.

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