New clues to treat tumours
A study by a team from Addenbrooke’s and the Wellcome Sanger Institute has revealed more about the origin of germ cell tumours, usually found in the ovaries and testicles, suggesting new approaches to future treatment.
The new research has found that even though these tumours can arise at different ages and can contain multiple cell types, their origins can often be traced back to a genetic event that happened in the womb.
In addition to this, these tumours use similar pathways of growth as normal tissues which could represent a potential target for treatment.
The research, published today (11 August 2022) in Nature Communications, also observed that tumours which develop before puberty carry distinct mutational signatures.
While further investigation is needed, these could be used in the future to help inform clinical decisions when it comes to treating children with germ cell tumours.
Max Williamson, now 24, was diagnosed with testicular cancer at Bedford Hospital when he was 15 years old.
Max said:
"I was referred to Addenbrooke's for treatment. I had no history of cancer in my family.
"Whilst an operation removed the primary cancer, it rapidly spread to the lymph nodes in my abdomen and I had to undergo three courses of chemotherapy.
“For me, an important part of experiencing cancer was trying to answer questions like ‘Why me?’ What happened to this part of my body to cause cancer?
"Nine years on, it’s so great to see the Cambridge team who looked after me (and many other researchers across the world) continuing to answer this question.”
Malignant germ cell tumours can appear at any age and are one of the most common cancers of adolescent and young men.
They also account for 5 per cent of all childhood cancers, with around 45 children being diagnosed every year in the UK.
Germ cell tumours can be made up from a variety of cell types, including muscle, placenta or teeth and hair in some cases.
The cell types that the tumour is composed of has implications for the prognosis, as some can be more aggressive than others. This study looked at how these tissues develop together within tumours, and contrasts them with how healthy tissues grow, which has not previously been possible.
Professor Matthew Murray, co-author on the paper and co-chair of the Biology Committee for the Malignant Germ Cell International Consortium, said:
“Max had a malignant germ cell tumour, which is the leading adult cause for average years of life lost per person dying of cancer. When Max’s tumour changed from localised to metastatic - with the rapid spread to his lymph nodes – his treatment had to be urgently changed from follow-up surveillance to chemotherapy.”
“This study, which analysed both the DNA and RNA, found little relationship between the tissues the tumour made – what we can see down the microscope – and the changes found in the genetic code.
"Clearly, the tissue’s appearance doesn’t tell the whole story and underlines the needs for additional molecular tests that can accurately predict a tumour’s behaviour. The genetic patterns observed in this study are also a significant step forward in our understanding of these tumours, which, with more research, will aim to improve and personalise treatment of this type of cancer for patients like Max.”
In this new research, scientists from the Wellcome Sanger Institute, Cambridge University Hospitals NHS Foundation Trust, and their collaborators, examined tumour samples from 15 individuals.
By applying in-depth genetic sequencing techniques, they were able to study the DNA and RNA of all the different tissues they sampled within the tumours at an unprecedented resolution.
By analysing this extensive amount of genetic information, the team were able to trace the origin of the tumours all the way back to the beginning of their development in the womb.
They found that the way tumours created tissues, such as cartilage or muscle, shared similarities with how those are created in a growing embryo which may represent novel treatment targets.
The researchers also identified different mutational signatures in tumours of young children compared with tumour samples taken from older children, over the age of 12.
Therefore, the mutational signatures the team found could be used as a future biomarker that allows healthcare professionals to identify which course of chemotherapy is the most appropriate based on the cancer’s genetic makeup.
This could prove particularly useful for children who develop these tumours around the current age cut-offs which determine the treatment they receive.