Published today (7th March) in Cell, the resource will enable scientists to study what causes mutations that lead to the development of cancer, directly in human cancer cells. Further understanding into these mutational processes could help researchers find novel avenues for research towards cancer prevention and treatment.
All cancers are caused by DNA mutations, and these mutations form molecular fingerprints in the DNA called mutational signatures. More than 50 different signatures have been found, many of which are caused by external factors, for example ultraviolet light exposure or tobacco smoking. Others are due to factors inside the cell such as the failure of DNA repair mechanisms. However, the causes of many mutational signatures are unknown and they are extremely challenging to study experimentally.
Researchers - Sequences - Cancer - Cell - Lines
The researchers studied the genome sequences of 1,001 human cancer cell lines and 577 grafts of human cancers*, including the most widely used models in cancer research and therapeutics testing. They used all the known mutational signatures and catalogued which signature is present in each cancer model. This resource then allowed the scientists to choose specific cell lines and study how each mutational pattern changed over time in cancer cells.
They found that mutational signatures from known external factors like smoking or UV light stopped being created in cell lines, whereas most signatures associated with factors inside the cell continued to be generated, and at a steady rate. Surprisingly however, they discovered that two common mutational signatures associated with a DNA editing protein known as APOBEC, actually switched on and off over time in cell lines, a phenomenon they called "episodic mutagenesis."
APOBEC - DNA - Enzymes - Part - Innate
APOBEC DNA editing enzymes are part of the innate immune system, protecting us from infections by causing mutations in viruses such as HIV, leaving APOBEC mutational signatures in the viral genomes. APOBEC-like signatures are a major mutation pattern in...
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