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Century-old tumours could shed light on rare childhood cancers

Boxes containing old tumours preserved in paraffin wax.
Boxes containing old tumours preserved in paraffin wax. Photograph: John Stead

A collection of almost 100-year-old tumour samples has revealed genetic mutations that scientists believe could be responsible for some of the rarest forms of childhood cancer.

The findings, by pathologists at Great Ormond Street hospital, could eventually lead to more effective treatments for uncommon forms of the disease, including cancer of the blood vessels and muscles.

The most significant element of the work is the surprise discovery that genetic information could be readily obtained from samples that had been sitting in a hospital vault for almost a century.

An ability to mine hospital archives would drastically increase the availability of rare tumour samples, allowing scientists to uncover for the first time which genes are driving these cancers.

Neil Sebire, a pathologist at the hospital, who led the work, 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.”

The Post Mortem and Case book
The Post Mortem and Case book. An ability to mine hospital archives would increase the availability of rare tumour samples. Photograph: John Stead

Until now, the lack of available data has meant patients with rare cancers have not benefited from the major advances in cancer genetics during the past decade that have led to targeted drugs, such as herceptin for breast cancer.

Sam Behjati, a co-author and paediatric registrar based at Addenbrooke’s hospital in Cambridge, said: “For very rare tumours we know almost nothing, we just go on a fishing exercise and see what we find.”

The latest study could almost instantly change this picture. With the problem of rare cancers in mind, the Great Ormond Street team decided to investigate how far back into the hospital’s archive they could obtain DNA sequences.

The hospital was founded in 1852, largely thanks to donations raised by the author Charles Dickens. Its patient records, complete with tumour samples, date back the full 165 years.

However, the team selected samples from the 1920s, when medical terminology became more easily comparable to modern diagnoses. Previously, the oldest tumour sample to be genetically sequenced was 32 years old.

“To be honest I wasn’t entirely convinced it was going to work,” said Behjati. “I was gobsmacked because the data was so good. It was very surprising.”

The team picked three cases involving children who had undergone surgery at the hospital for a muscle tumour, bone marrow cancer and a blood vessel tumour. As a routine part of record-keeping, tumour samples were taken during surgery, soaked in formaldehyde and the slivers of tissue preserved in small cubes of paraffin wax.

An old tumour preserved in paraffin wax.
Scientists discovered that genetic information could be readily obtained from samples. Photograph: John Stead

In the case of the blood vessel tumour, scientists identified a mutation that is known to be involved in certain leukaemias, but not previously associated with solid tumours. The findings are published in a letter in the Lancet Oncology journal.

The team hope to conduct a more targeted search of the archive aimed at identifying key mutations in a variety of rare cancers. In some cases, they anticipate the mutations involved may match those seen in more common cancers, meaning these patients would benefit from existing drugs.

“It could help children, if they have a mutation where there’s a drug,” said Behjati. “It could make a real difference for the future.”

Prof Jane Maher, joint chief medical officer at Macmillan Cancer Support, welcomed the findings. “Being diagnosed with cancer is tough. Being diagnosed with a rare cancer, where there are fewer experts and less information about the best treatments, is really tough,” she said.

“It is simply not fair that someone with a rarer cancer should be worse off than those with more common forms of the disease, so it’s great to see these steps in the right direction.”

This article titled "Century-old tumours could shed light on rare childhood cancers" was written by Hannah Devlin Science correspondent, for on Thursday 18 May 2017 05.44pm


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