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RNA sequencing detects fusion genes in childhood cancer

A new study, carried out by scientists from the Princess Máxima Centre, has shown that RNA sequencing can identify more fusion genes in cancer patients than traditional methods.

Fusion genes and cancer

For many years, fusion genes have been known to play a role in cancer. As the name suggests, fusion genes are formed when two previously independent genes join together to create one new gene. Fusion genes are often faulty and produce abnormal proteins. Therefore, they are usually oncogenic and play a significant role in cancer development. Their clinical relevance means the identification of fusion genes is key for accurate cancer diagnosis and treatment.

However, current methods for detecting fusion genes are limited. Reverse transcription polymerase chain reaction (RT-PCR) assays lack the flexibility to detect rare gene fusions. In addition, genome-wide approaches, such as karyotyping, have limited resolution. Therefore, scientists clearly require a new identification method.

To address this issue, the team behind the new study, published in JCO Precision Oncology, investigated the efficiency of whole transcriptome RNA sequencing (RNA-seq) at identifying gene fusion events.

RNA sequencing of tumours

First, the team sequenced the entire RNA of tumour tissue samples from 244 children with cancer. In total, the results identified 78 clinically relevant fusion genes. In comparison, traditional diagnostic methods only identified 55. Even within these 55, the traditional methods often only reveal 3’ fusion partner and not the 5’ partner. The identification of both is important clinically, as specific fusion partnerships can determine the diagnosis. Therefore, you need to know both original genes. These results suggest that RNA-seq is a superior technique for gene fusion identification.

Fusion gene identification leads to improved treatment

In some cases, the identification of additional fusion genes by RNA-seq actually changed the diagnoses of the patients. Doctors thought that one young girl had dermatofibrosarcoma protuberans, a rare type of skin cancer. However, RNA-seq identified a specific fusion gene in her tumour sample. This revealed that her cancer was, in fact, infantile fibrosarcoma. Researchers then enrolled the patient on a clinical trial for a new targeted drug specific to her disease. 

Future work

Overall, the results of this study illustrate the clear advantages of using RNA-seq over traditional methods as a technique to identify fusion genes. However, there are still some limitations to RNA-seq, such as a longer turnaround time and a need for relatively large samples of RNA. Despite this, RNA-seq still appears to perform better than current methods. In fact, the Princess Máxima Centre in the Netherlands is currently using RNA-seq to identify fusion genes in all their cancer patient samples.

Co-leader of the study, Dr Patrick Kemmeren said:

“In this study, we show that a single test that searches the entire tumour RNA is almost one and a half times more sensitive to genetic faults in childhood cancer. I expect that the test we have developed will replace the various traditional methods in the foreseeable future.”

Fellow co-leader, Dr Bastiaan Tops, said:

“Because we can look at the full genetic landscape of a child’s tumour at diagnosis, we can discuss possible consequences for treatment with the child’s doctor right away. That means we can offer children with cancer the very best opportunities, based on the latest scientific insights.”

Picture credit: Canva


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Cancer / RNA sequencing / Tumour