A collection of century old tumour samples held at Great Ormond Street Hospital (GOSH) has helped shed light on the genetic mutations that cause some of the rarest childhood cancers.
Stored in the GOSH archive are hundreds of case books containing information collected from surgery and postmortem examinations going back to when GOSH was founded in 1852. Alongside these many hand and typewritten records are tumour samples preserved in small blocks of paraffin wax.
Looking to the past to research rare diseases
The lead researcher Professor Neil Sebire, Consultant Pathologist at GOSH and Reader in Paediatric and Development Pathology at the UCL Great Ormond Street Institute of Child Health, said, “When the disease is so rare that even if you collected every case you’d still only have three or four cases a year, it might take you 50 years to get enough cases to determine which mutations are important.” Analysing archived samples could therefore increase the pool of information available on these rare conditions and help researchers design more targeted treatments for the most uncommon forms of cancer.
By painstakingly matching up patient records and tumour samples, the research team was able to identify samples of tissue from children who had undergone surgery at GOSH for three rare types of cancer – including a muscle cancer called rhabdomyosarcoma. The team focussed on samples from the 1920s as by this period the medical descriptions in the case books were more comparable to medical terminology used nowadays.
The next step was for the researchers to extract the DNA from the samples and then use powerful modern methods to obtain the genetic sequence. Together this information enabled researchers to identify several cancer causing mutations. In one sample of a blood vessel cancer called haemangioma, the team found a new mutation which had previously only been seen in leukaemia and lymphoma.
This work has shown for the first time that it is possible to obtain genetic information from century old preserved tissue. Previously the oldest sample that had been sequenced was 32 years old. Given the lack of available tissue samples for very rare conditions, the research shows that archived samples are potentially an untapped resource to help increase the number of samples available for research. This could pave the way for the development of more effective treatments for these diseases.
Research at GOSH
The study was supported by the National Institute of Health Research GOSH Biomedical Research Centre and carried out in collaboration with the Wellcome Trust Sanger Institute.Find out more about the pioneering research taking place at GOSH.