Expert Commentary: Insights into Cancer Mutation Patterns

Researchers at Rutgers Cancer Institute of New Jersey provided expert commentary on a study exploring how changes in the structure and packaging of DNA, known as chromatin remodeling, influence the mutation patterns seen in cancer. The commentary was published online today in Nature Cancer.

Background

Previous studies have shown that different regions of the genome mutate at different rates in tumors, but it's not fully understood how chromatin remodeling, which is the process of modifying the structure of DNA and its proteins to regulate which genes can be turned on or off within a cell, contributes to these variations. Researchers analyzed mutation data from thousands of tumor genomes. 

Findings

• Researchers identified 13 distinct patterns of mutation density across the genome, some specific to certain tissues and others common across various types of cancer
• One significant pattern, called RMDglobal1, was linked to changes in facultative heterochromatin, a type of chromatin associated with flexible DNA replication and remodeling
• Another pattern, RMDglobal2, was associated with mutations in the TP53 gene, which is frequently mutated in cancer

Subhajyoti De, PhD, researcher at Rutgers Cancer Institute and an associate professor of pathology and laboratory medicine at Rutgers Robert Wood Johnson Medical School, shares his insight

• Emphasizes the importance of chromatin remodeling in influencing the distribution of mutations in cancer genomes
• Discusses the potential clinical implications of the findings, particularly in predicting the extent of chromatin remodeling during tumorigenesis
• Highlight that genomic rearrangements or mutations in epigenetic modifier genes can impact chromatin remodeling, which, in turn, can alter patterns of mutation density across the cancer genomes
• Genomic and epigenomic alterations influence one another, which need to be taken into account while interpreting the changes in cancer genomes during tumor development
• Points out the broader significance of the research findings in advancing understanding of DNA damage and repair mechanisms at the chromosomal domain level

Dr. De is available for additional comment.