This article is more than 5 years old. Information may no longer be current.
Findings offer insights into mutational processes that lead to cancer development
Click Here to Manage Email Alerts
An analysis of several million mutations provided unprecedented details that may shed light on the underlying causes of cancer development.
Researchers aimed to investigate the biological processes that the cause somatic mutations that ultimately lead to malignancy. Through an analysis of 4.9 million mutations from 7,042 cancers, they were able to extract 21 mutational signatures.
Results demonstrated that two or more signatures are present in each disease, highlighting the diversity of processes that cause cancer. For example, ovarian cancer involves two mutational processes, whereas there are six associated with liver cancer development.
A signature attributed to the APOBEC family of cytidine deaminases was present in a number of cancers. However, other signatures were malignancy-specific.
The analysis also revealed that some signatures might carry associations with age at diagnosis, known mutagenic exposures or defects in DNA maintenance.
The findings indicated that 25 of 30 cancers that underwent analysis contained signatures from mutational processes associated with increased age. Other signatures failed to demonstrate any point of origin.
The researchers also observed evidence of kataegis, or hypermutation localized to specific genomic regions.
Although the mechanistic basis of some signatures is starting to become clearer, it remains unknown for many others, researcher Michael Stratton, MD, PhD, director of the Wellcome Trust Sanger Institute, and colleagues wrote.
“Elucidating the underlying mutational processes will depend upon two major streams of investigation,” Stratton and colleagues wrote. “First, compilation of mutational signatures from model systems exposed to known mutagens or perturbations of the DNA maintenance machinery and comparison with those found in human cancers. Second, correlation of the contributions of mutational signatures with other biological characteristics of each cancer through diverse approaches ranging from molecular profiling to epidemiology. Collectively, these studies will advance our understanding of cancer etiology with potential implications for prevention and treatment.”
Disclosure: The researchers report no relevant financial disclosures.
Click Here to Manage Email Alerts