Scientists have uncovered new genetic errors and evolutionary patterns that play a role in the development of testicular cancer. Their research provides valuable insights into how this disease develops and potential strategies for treatment. Key discoveries from the study include:
– New potential cancer drivers linked to testicular cancer, some of which are specific to certain subtypes, allowing for better patient stratification based on tumor traits.
– A reconstruction of the evolutionary paths of genetic changes and likely progression routes in testicular germ cell tumors (TGCTs).
– A wider variety of mutational signatures linked to TGCT, which represent unique patterns of DNA damage influenced by factors like smoking and UV exposure, and which offer a historical perspective on cancer risk linked to these exposures.
Scientists have uncovered new genetic errors and evolutionary patterns that play a role in testicular cancer. Their research provides valuable insights into how this disease develops and potential strategies for treatment.
Testicular cancer constitutes about 1% of all male cancers and is notably the most frequent cancer among men aged 15 to 44. In Ireland, close to 200 men are diagnosed with this cancer each year, with a rise in incidence rates noted in both Northern and Central Europe recently.
Fortunately, when diagnosed early, testicular cancer is highly treatable, boasting survival rates over 90%. Nevertheless, patients with the most severe forms of the disease have a much lower prognosis, with roughly a 50% survival rate despite rigorous clinical trials. Current chemotherapy treatments also come with considerable toxicity and side effects.
Utilizing data from the 100,000 Genomes Project, spearheaded by Genomics England and NHS England, the researchers conducted whole genome sequencing (WGS) on samples from 60 patients to answer key unresolved biological and clinical questions concerning testicular germ cell tumors (TGCTs). Their findings have been published in the influential international journal Nature Communications.
Among the significant findings are:
- New potential cancer drivers in testicular cancer, including some linked to specific subtypes, which may assist in categorizing patients based on their tumor characteristics.
- A reconstruction of the evolutionary paths of genetic changes and likely progression routes in TGCT.
- Discovery of a wider range of mutational signatures related to TGCT, unique DNA damage patterns indicative of various carcinogenic exposures (like smoking and UV light), allowing for retrospective assessment of exposure-related cancer risks.
- Identification of recurrent mutation hotspots in testicular cancer that were previously unrecognized.
- Recognition of a unique genomic immune mechanism related to TGCT, primarily seen in seminomas, which is the most common tumor subtype.
Máire Nà Leathlobhair, the study’s first author and Assistant Professor at Trinity College Dublin’s School of Genetics and Microbiology, stated: “We have made significant progress in comprehending the development of this disease and gained crucial insights into potential treatment options, which are vital for improving patient outcomes.”
“Critically, this research was made possible through the valuable contribution of tissue samples from participants in the 100,000 Genomes Project and the collaborative efforts of NHS healthcare professionals. This marks one of the first substantial landscape studies on testicular cancer employing a robust whole genome sequencing approach, which was pivotal in revealing insights that other methods may have missed.”
“Our goal was to turn genomic knowledge into tangible patient benefits, connecting fundamental discoveries with practical applications, illustrating how extensive patient data and samples can enhance our understanding of a disease.”
This collaborative research initiative was led by senior authors Professors Matthew Murray, Andrew Protheroe, Clare Verrill, and David Wedge, and involved a dedicated group of researchers, clinicians, and trainees from both academic institutions and the NHS, with contributions from Trinity, the University of Oxford, the University of Cambridge, and the University of Manchester.
To deepen their understanding of the disease, the researchers aim to recruit more participants to encompass a broader range of outcomes, ethnic backgrounds, and types of testicular cancers.
