DNA code with Nasopharyngeal carcinoma cell under microscopy
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Malignant germ cell tumors can appear at any age and are one of the most common cancers of adolescent and young men, accounting for five percent of all childhood cancers. Now, scientists have discovered 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 that happened in the womb. In addition, say the researchers that included scientists from the Wellcome Sanger Institute, Cambridge University Hospitals NHS Foundation Trust, and other collaborators, these tumors use similar pathways of growth as normal tissues which could represent a potential target for treatment.

The research, published today in Nature Communications, also observed that tumors which develop before puberty carry distinct patterns of mutations, or mutational signatures. These signature could be used in the future to help inform clinical decisions when it comes to treating children with germ cell tumors.

“We are excited to find genetic features that can be used to distinguish the tumors so clearly,” said Thomas Oliver, Ph.D., co-first author from the Wellcome Sanger Institute and Cambridge University Hospitals NHS Foundation Trust. “Clinically, treating teenage and young adult patients can be challenging as they fall between pediatric and adult treatment protocols. It is important to treat them sufficiently but not excessively to avoid long-term side effects, so getting the intensity of the chemotherapy right is important.

“Our research suggests that the genetic makeup of the tumor might be used to help categorize such patients, which will hopefully result in children, and indeed all patients with germ cell tumors, getting the most appropriate therapy in the future.”

For this study, the scientists used in-depth genetic sequencing to examine tumor samples from 15 individuals and were able to collect both the DNA and RNA data of all the different tumor tissues they sampled at very high resolution.

Through analysis of the DNA and RNA sequences the investigators found they could trace the origins of tumors to their original development in the womb. They found that the way tumors created tissues, such as cartilage or muscle, shared similarities with how those are created in a growing embryo. The scientist are hopeful this information could be used to discover and develop dug against what are likely novel treatment targets.

“Germ cell tumors affect around 45 children in the U.K. every year. However, they can also develop at any age. Interestingly, our research found that early development signals, those which you see while a fetus is developing in the womb, can be found in these tumors,” said co-senior author Sam Behjati, Ph.D., of  the Wellcome Sanger Institute and Cambridge University Hospitals NHS Foundation Trust. “In the future, it may be possible to target these, as is done in some blood cancers, to give a new type of therapy for those with this type of cancer.”

While more study is needed and potential treatments targeting these signatures are likely years away, the research has already benefited some patients. Max Williamson, who is now 24, was diagnosed with testicular cancer at Bedford Hospital when he was 15 years old.

“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,” Williamson said.

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