Algorithm developed to identify vulnerable tumours

An algorithm called PRRDetect has been developed to identify immunotherapy-susceptible cancers.

Using data from the NHS 100,000 Genomes Project (see BioNews 979), scientists from the University of Cambridge, have developed a novel, highly sensitive and specific mutation-detection algorithm. This allowed them to identify tumours with unusual patterns of key mutations, called insertion/deletions (indels), in which letters are inserted or deleted from the normal DNA sequence. These can result from a fault in DNA repair called post-replicative repair dysfunction (PRRd).

'Cancers with faulty DNA repair are more likely to be treated successfully. PRRDetect helps us better identify those cancers and... it could ultimately help doctors better tailor treatments to individual patients,' said Professor Serena Nik-Zainal, from the University of Cambridge and lead author of the study.

Publishing their findings in Nature Genetics, the team has built on earlier research by Professor Nik-Zainal where her team analysed the whole genomes of approximately 12,000 tumours (see BioNews 1141) and also devloped the MMRDetect algorithm to identify DNA repair defects among tumour cells (see BioNews 1093).

Now, by analysing the whole genome sequences of nearly 5000 tumours from seven types of cancer known to generate a higher number of tumours with PRRd, including bowel, brain, endometrial and skin, they developed a new classification algorithm to detect and examine specific patterns of indels.

They identified 37 different patterns of indels. Ten of the indel patterns were already linked to known causes of cancer, such as UV exposure or smoking, but eight were unambiguously correlated with PRRd.

As PRRd tumours are more vulnerable to a type of cancer treatment called immunotherapy, which recruits the body's own immune system to help fight cancer, the team hopes that the PRRDetect algorithm could be used to identify cancers that are more immunotherapy-sensitive.

'Genomic medicine will revolutionise how we approach cancer treatment. We can now get full readouts of tumour DNA much more easily, and with that comes a wealth of information about how an individual's cancer can start, grow and spread,' said Dr Iain Foulkes, from Cancer Research UK, who was not involved in the research. 'Tools like PRRDetect are going to make personalised treatment for cancer a reality for many more patients in the future. Personalising treatment is much more likely to be successful, ensuring more people can live longer, better lives free from the fear of cancer.'

Currently, the team aims to take PRRDetect into clinical trials and expand the number of cancer types studied.

Professor Nik-Zainal concluded: 'To use genomics most effectively in the clinic, we need tools which give us meaningful information about how a person's tumour might respond to treatment... We are getting closer to the point where getting your tumour sequenced will be as routine as a scan or blood test.'