Kataegis

A phenomenon of localized hypermutation in cancer genomes

Kataegis is a phenomenon characterized by clusters of localized hypermutation occurring in certain regions of the genome, often observed in cancer cells. This term is derived from the Greek word "καταιγίς" meaning "thunderstorm," reflecting the "storm" of mutations that occur in these localized regions.

Characteristics

Kataegis is typically identified by the presence of multiple somatic mutations in close proximity on a single chromosome. These mutations are often cytosine to thymine transitions, which are indicative of the involvement of the APOBEC family of enzymes. The mutations are usually found in regions of the genome that are undergoing DNA replication or DNA repair.

Rainplot showing kataegis in a breast cancer genome

Mechanism

The underlying mechanism of kataegis is thought to involve the activity of the APOBEC family of cytidine deaminases. These enzymes can deaminate cytosine bases in single-stranded DNA, converting them to uracil, which is then replaced by thymine during DNA replication. This process results in a high frequency of C>T mutations in the affected regions.

APOBEC enzyme structure

Kataegis is often associated with regions of the genome that are undergoing DNA double-strand break repair, particularly through the error-prone non-homologous end joining (NHEJ) pathway. The presence of single-stranded DNA during these processes provides a substrate for APOBEC enzymes, leading to localized hypermutation.

Biological Significance

Kataegis has been observed in various types of cancer, including breast cancer, lung cancer, and lymphoma. The presence of kataegis can influence the tumor microenvironment and contribute to tumor evolution by generating genetic diversity within the cancer cell population. This diversity can lead to the emergence of drug resistance and metastasis.

Research and Implications

Understanding kataegis and its role in cancer development is an active area of research. By studying the patterns of mutations and the enzymes involved, researchers aim to develop targeted therapies that can mitigate the effects of kataegis and improve cancer treatment outcomes.

Error-prone translesion synthesis DNA polymerase

Related pages

• APOBEC3A
• DNA repair
• Somatic mutation
• Cancer genomics