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The largest single-cell study to date in childhood cancer, neuroblastoma, answered important questions about the genesis of the disease. Researchers from the Wellcome Sanger Institute, Great Ormond Street Hospital (GOSH), and the Princess Máxima Center for Pediatric Oncology, have found that all neuroblastomas originate from a single type of embryonic cell called sympathoblasts.
The study, published today (February 5, 2021) in Scientific advances, sought to understand why neuroblastomas vary in severity, with some easy to treat and others with relatively low five-year survival rates. The fact that all neuroblastomas originate from sympathoblasts makes them an attractive drug target, as these cells only exist in the tumor after childbirth.
Neuroblastoma is a rare cancer that usually affects children under the age of five. It begins in the abdomen, usually in the adrenal glands – hormone-producing glands located above the kidneys. Neuroblastoma is remarkable in that its severity can vary greatly from individual to individual. In some children the cancer will go away without treatment, while in others the cancer is relentless. The five-year survival rate for neuroblastoma is one of the lowest of all childhood cancers *.
This varied perspective prompted researchers to question whether the range of severity could be caused by neuroblastomas from different types of cells at different stages of a child’s development in the womb. This was made possible by the advent of single-cell mRNA sequencing, a high-resolution technology that can identify different types of cells present in tissue based on genes expressed by individual cells.
In this study, the gene expression of 19,723 cancer cells was analyzed and compared to a benchmark of 57,972 developing adrenal cells in the hopes of identifying the cell types from which neuroblastomas originate and finding new ones. treatment targets.
Dr Jan Molenaar, lead author of the Princess Máxima Center for Pediatric Oncology in the Netherlands, said: “What is most striking about our results is that despite the great diversity in behavior clinical neuroblastoma, there is an overall neuroblastoma cell. found in all patients. Identifying sympathoblasts as the root of any neuroblastoma is an important step in understanding how the disease develops and, hopefully, how we can treat it. “
Currently, many cancer treatments have serious side effects for the patient. But in recent years, technological advancements have accelerated drug development by enabling researchers to identify differences between biological processes, such as the expression of a particular gene, within healthy human cells and those within. cancer cells. These differences can be exploited to attack cancer cells without affecting the healthy cells of the patient.
The presence of sympathoblasts, a type of developmental cell that is not normally found in children after birth, makes them a promising drug target for the treatment of neuroblastoma.
Dr Karin Straathof, lead author of the Great Ormond Street Hospital study, said: “Neuroblastoma is an unusual cancer in that some tumors go away without intervention, but the disease still has one of the survival rates. at five years lowest of all childhood cancers. This study fills important gaps in our knowledge about what neuroblastoma cells are and has revealed new treatment targets. My hope is that new, less intrusive therapies can be developed targeting sympathoblasts, a type of developmental cell that only exists in neuroblastoma tumors after a child is born. “
In addition to facilitating the discovery of sympathoblasts as the root of neuroblastoma, the single-celled reference map of the developmental adrenal gland will also contribute to the Human Cell Atlas ** project. The project aims to create comprehensive reference maps of all human cell types – the fundamental units of life – as a basis for understanding human health and diagnosing, monitoring and treating disease.
Dr Sam Behjati, lead author of the Wellcome Sanger Institute and Cambridge University Hospitals study, said: “Our study shows the power to examine individual childhood cancer cells to reveal not just one, but one. plethora of innovative treatment ideas. raises the exciting prospect that a single cell atlas of all types of pediatric tumors can transform our understanding of childhood cancer. “
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Contact details:
Dr Matthew Midgley
Press office
Wellcome Sanger Institute
Cambridge, CB10 1SA
Phone: 01223 494856
Email: [email protected]
Notes to Editors:
* More information on neuroblastoma is available from Cancer Research UK:
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** More information on the Human Cell Atlas (HCA) project is available here:
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Publication:
Gerda Kildisiute, Waleed M. Kholosy, Matthew D. Young et al. (2021). Comparisons between the tumor and normal single-celled mRNA reveal a pan-neuroblastoma cancer cell. Scientific advances. DOI: https: /
Funding:
This study was funded by Wellcome. Additional funding has been received from the St Baldrick’s Foundation and the National Institute for Health Research (NIHR).
Selected websites:
About the Princess Máxima Center
Each year, around 600 children in the Netherlands are diagnosed with cancer. One in four children with cancer still die from the disease.
In order to cure children of cancer, all care and research in the Netherlands is concentrated in the Princess Máxima Center for Pediatric Oncology in Utrecht. More than ten years ago, parents and healthcare professionals took the initiative. The new pediatric oncology center was opened by Queen Máxima of the Netherlands on June 5, 2018.
The mission of the Princess Máxima Center is to cure every child with cancer, with an optimal quality of life. The Princess Máxima Center is the largest pediatric oncology center in Europe where care and research are closely linked. Around 400 scientists and more than 800 healthcare professionals work closely together.
About the research at Great Ormond Street Hospital
Great Ormond Street Hospital is one of the world’s leading children’s hospitals with the widest range of dedicated children’s health specialists under one roof in the UK. The hospital’s pioneering research and treatment gives hope to children across the UK with the rarest, most complex and often fatal diseases. All research at the Great Ormond Street Hospital NHS Foundation Trust and UCL Great Ormond Street Institute of Child Health is made possible by the NIHR Great Ormond Street Hospital Biomedical Research Center.
The Wellcome Sanger Institute
The Wellcome Sanger Institute is a leading genomics research center in the world. We undertake large-scale research which forms the foundation of knowledge in biology and medicine. We are open and collaborative; our data, results, tools and technologies are shared around the world to advance science. Our ambition is vast – we undertake projects that are not possible anywhere else. We use the power of genome sequencing to understand and harness the information contained in DNA. Funded by Wellcome, we have the freedom and support to push the boundaries of genomics. Our results are used to improve health and understand life on Earth. For more information, see http: // www.
About Wellcome
Wellcome exists to improve health by helping great ideas thrive. We support researchers, we take on great health challenges, we campaign for better science, and we help everyone get involved in health science and research. We are a politically and financially independent foundation.
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