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Brain tumours in children with biallelic mismatch repair deficiency (bMMRD) show an unprecedented degree of mutation, according to results from a new study. The researchers used exon and genome sequencing for 17 inherited cancers from 12 patients with bMMRD. They compared the results with a reference dataset comprising more than 7000 cancers. They discovered that malignant bMMRD brain tumours have about 600 mutations per cell division. Within 6 months, these tumours amass roughly 20 000 exonic mutations, far more than any other cancer within the dataset. The findings have immediate diagnostic implications. “If we see 20 000 mutations in a patient’s tumour, it has to be bMMRD”, explains senior author Uri Tabori (The Hospital for Sick Children, Toronto,

ON, Canada). “So we can then screen all the individuals in their family—we already know that we can improve survival by finding the tumour early”. The investigators noted that patients with bMMRD did not have many germline mutations, which implied that something was happening within the tumour itself. The genetic driver turned out to be a pair of polymerase mutations. Taken in tandem with the malfunctioning mismatch repair pathway, this means that patients lose all ability to repair DNA each time a cell divides. “The system is overwhelmed by mutations”, Tabori told The Lancet Oncology. But his team also found that once the mutations had reached a certain threshold, the tumour cell expired. This could point the way to a possible therapy. Katharina Wimmer (Medical University of Innsbruck,

Innsbruck, Austria) commented that “the study bears the good news that there is a rationale for mutation increasing drugs; however, the sad news of the study is that these brain tumours develop so rapidly that surveillance becomes even more difficult than previously thought”. A subgroup of colon and endometrial cancers, and gliomas show the same type of mutations as bMMRD brain tumours. “Adult cancers that have the same mutation signatures will behave similarly and can be treated similarly—that could be a large number of cancers”, points out Tabori. Alongside continuing to study the mutation phenotype, his group is currently recruiting for a clinical trial to treat cancers in children with bMMRD.

Alfred Pasieka/Science Photo Library

Large degree of mutation in paediatric brain tumours

Published Online February 13, 2015 http://dx.doi.org/10.1016/ S1470-2045(15)70067-7 For the study by Shlien and colleagues see Nature Genetics 2015; published online February 2. DOI:10.1038/ng.3202

Talha Khan Burki

HPV vaccination unlikely to promote risky sexual behaviours Human papillomavirus (HPV) vaccination is not associated with increased rates of sexually transmitted infections (STIs) in females, suggests a new study. According to the study investigators, it is unlikely that HPV vaccination promotes unsafe sexual activity. Although HPV has a widespread prevalence in the USA, in 2008, only 37% of females aged 13–17 years had received at least one dose of HPV vaccination, and 18% had received all three recommended doses. By 2013, the figures rose to 57% and 38%, respectively. “A minority of girls and boys in the USA receive the recommended [HPV] vaccine dose, and one reason for this may be concerns that use of the vaccine could increase sexual activity”, commented investigator Seth Seabury (University of Southern California, LA, USA). “However, this concern does not appear to be supported by the data.” www.thelancet.com/oncology Vol 16 March 2015

The researchers analysed a large database of insurance claims during Jan 1, 2005, to Dec 31, 2010, and assessed whether HPV vaccination was associated with an increase in STIs in girls aged 12–18 years who received vaccination (n=21 610) compared with matched non-vaccinated girls (n=186 501). In the year before HPV vaccination, the rates of STIs were higher in vaccinated girls (94 of 21 610; 0·43%), than in nonvaccinated females (522 of 186 501; 0·28%) (odds ratio [OR] adjusted for age 1·37, 95% CI 1·09–1·71; p=0·007). In the year after vaccination, the STI rates increased in both vaccinated (147 of 21 610; 0·68%) and nonvaccinated girls (781 of 186 501; 0·42%) (adjusted OR 1·50, 95% CI 1·25–1·79; p

Large degree of mutation in paediatric brain tumours.

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