New research has detailed the origins of germ cell tumours, which are derived from the cells that give rise to sperm or eggs. The results shed light on how these tumours develop, and reveal possible future avenues for novel therapies.
Image credit: Fernando Zhiminaicela via Pixabay, free licence
Scientists from the Wellcome Sanger Institute, Cambridge University Hospitals NHS Foundation Trust, and collaborators uncovered that even though these tumors appear at different ages and can contain multiple cell types, their mutational origins can often be traced back to a genetic event happened in the womb. In addition to this, these tumours utilise similar pathways of growth as normal tissues which could represent a potential target for treatment.
The research, published in Nature Communications, also observed that tumours which develop before puberty carry distinct patterns of mutations, known as mutational signatures. While further investigation is needed, these could be used in the future to help inform clinical decisions regarding treating children with germ cell tumours.
Malignant germ cell tumours can appear at any age and are one of the most common cancers of adolescent and young men1. They also account for approximately 5 per cent of all childhood cancers2, with around 45 children being diagnosed every year in the UK3.
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.
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 team's mutational signatures 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 determining the treatment they receive.
Source: Sanger Institute