For the first time, scientists have systematically studied the genetic impact of chemotherapy on healthy tissue. Researchers from the Wellcome Sanger Institute, University of Cambridge, Cambridge University Hospitals NHS Foundation Trust (CUH) and their colleagues analyzed the blood cell genomes of 23 patients of all ages who had received different types of chemotherapy.

Published in Nature Genetics, the findings show that many, but not all, chemotherapy drugs cause mutations and premature aging in healthy blood.

As part of the Cancer Grand Challenges team Mutographs project, researchers have discovered new patterns of DNA damage, or mutational signatures, associated with specific chemotherapy drugs.

Chemotherapy is a type of anti-cancer treatment that destroys cancer cells. It is a systemic treatment, meaning it affects the entire body and can be administered as a single chemotherapy drug or in combination with other drugs.

It is estimated that in developed countries about 10% of the population has had chemotherapy for cancer and other diseases at some point in their lives.

Chemotherapy can have long-term side effects on healthy, non-cancerous tissue and is associated with an increased risk of secondary cancer. However, the biological mechanisms underlying these side effects have been poorly understood.

For the first time, scientists have systematically studied the genetic impact of chemotherapy on healthy tissue. Researchers from the Wellcome Sanger Institute, University of Cambridge, Cambridge University Hospitals NHS Foundation Trust (CUH) and their colleagues analyzed the blood cell genomes of 23 patients of all ages who had received different types of chemotherapy.

Published in Nature Genetics, the findings show that many, but not all, chemotherapy drugs cause mutations and premature aging in healthy blood.

As part of the Cancer Grand Challenges team Mutographs project, researchers have discovered new patterns of DNA damage, or mutational signatures, associated with specific chemotherapy drugs.

In developed countries, it is estimated that about 10% of the population has received chemotherapy for cancer and other diseases at some point in their lives. 

In a new study, scientists set out to examine the effects of chemotherapy on healthy blood. A team of mutographers from the Sanger Institute at the University of Cambridge (CUH) and their colleagues decided to study the blood because of the ease of sampling and the ability to culture the blood in the lab. In addition, the number of mutations in normal blood is very similar from person to person, providing a good baseline for determining whether it is higher in people who have received chemotherapy. The researchers sequenced the genomes of blood cells from 23 people aged three to 80 who had received chemotherapy for various blood cancers and solid cancers. 

Collectively, they were exposed to 21 drugs from all major classes of chemotherapy, including alkylating agents, platinum drugs and antimetabolites.

The results were compared with genomic data from nine healthy individuals who had never received chemotherapy.

By analyzing whole genome sequence data, the team found that many classes of chemotherapy drugs, but not all, actually cause more mutations in normal blood cells. For example, a three-year-old patient treated for neuroblastoma, a cancer of nerve tissue, had more mutations than 80-year-olds who had never received chemotherapy. By studying patterns of DNA damage known as mutational signatures, the researchers showed that different chemotherapy drugs have different mutational signatures and identified four new signatures found in patients who received chemotherapy.