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Hypermutation linked to chemotherapy

Thursday May 12th 2022

Chemotherapy may be one of the key reasons why some men pass on genetic mutations to their children, British scientists reported last night.

A research team at the Wellcome Sanger Institute, Cambridge, UK, investigated 'hypermutation', that is, cases of higher genetic mutation rates in children. They identified 12 children with this rare condition whose family genetic information was available.

The children had two to seven times more mutations than the general population. Analysis showed that most were carried in the sperm of the child's father, of whom just under half had previously been treated with chemotherapy - either platinum based drugs or alkylating agents.

Details are published in *Nature*. The authors explain that as hypermutation is rare, it could not have been caused by common factors such as smoking or pollution.

This is important information for patients who are offered chemotherapy, the authors point out, as they may opt to freeze their sperm for future use.

First author, Dr Joanna Kaplanis, said: “Our research analyses over 20,000 families and highlights new causes of these mutations, linking them back to germline mutations in the father’s sperm as well as identifying a new mutational signature.

"Understanding the impact of these germline mutations in the sperm could help us uncover why some people are more likely to have children with these high rates of random mutations and help protect against these if they cause disease.”

Co-author Professor Matthew Hurles added: “Chemotherapy is an incredibly effective treatment for many cancers, but unfortunately it can have some damaging side effects.

"These results require further systematic studies to see if there is a causal link between chemotherapy and sperm mutations."

Kaplanis, J. et al. Genetic and chemotherapeutic influences on germline hypermutation. *Nature* 11 May 2022; doi: 10.1038/s41586-022-04712-2

[abstract]

Tags: Cancer | Child Health | Genetics | Men's Health | UK News

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