The genetics revolution

All cancers are caused by changes inside cells that alter their DNA instructions, leading to uncontrolled cell division. Understanding how and when those genetic changes occur could lead to more rapid diagnostic techniques, predicting cancer risk or even, in future, stopping it from happening altogether.

“A decade ago, our primary diagnostic tool for cancer was looking at the cells under a microscope,” says Dr Darren Hargrave. “Genetics is revolutionising the way we diagnose and treat these and other diseases.”

“Studies have shown that for virtually every ‘type’ of cancer, there are many sub types, each with different genetic characteristics. That’s telling us incredibly valuable things about which existing treatments are likely to work for which types, as well as giving us new ideas for treatments.”

In 2018, Professor Hargrave launched a UK-wide project (SMPaeds) to sequence the DNA of all childhood tumours that have returned after treatment. These cancers are often resistant to further treatment and therefore have an extremely poor prognosis.

“We’re hoping to see the underlying instructions driving the cancer’s behaviour, including exactly how it puts up barriers against treatment. We’ll also look for genetic instructions that create unique features on the surface of cancer cells. That’s exciting because the more of those we have, the more we can target our treatments.”

2019 Professor Kathy Pritchard-Jones shows that genetic precursors to Wilms tumour can be found in healthy looking kidney tissue surrounding the tumour. Identifying where cancer may be ‘lying in wait’ could lead to more targeted surgery.

From 2019, the NHS is offering all children with cancer whole genome sequencing – analysis of their entire DNA sequence. In 2018, GOSH became one of seven Genomic Laboratory Hubs (GLHs) commissioned by the NHS to deliver this sequencing. The initiative builds on the 100,000 genomes project, a national initiative in which GOSH played a lead role.

GOSH is uniquely placed to drive this pioneering work forward. As of 2019, it is the most digitally advanced hospital in the UK, with a centralised electronic patient record system and linked analytics platform to enable pioneering research. The new Zayed Centre for Research into Rare Disease in Children houses state-ofthe-art facilities to support genetic research, including world-class gene and cell therapy laboratories.

Experts across GOSH are working closely with leaders in the field, from launching international clinical trials and partnering with organisations like Cancer Research UK, to collaborating with the Wellcome Sanger Institute, a world-leader in genetics that played an integral part in sequencing the first human genome.

Tomorrow

2019 As part of a national childhood cancer collaboration INSTINCT, Professor Thomas Jacques shows that molecules blocking DNA instructions from being read can provide key information about which treatments are likely to work.