The largest single cell study to date of childhood cancer, neuroblastoma, has answered important questions about the genesis of the disease. The researchers from the Wellcome Sanger Institute, Great Ormond Street Hospital (GOSH) and the Princess Onxology Center for Pediatric Oncology, found that all neuroblastomas arise from one type of embryonic cell called sympathoblasts.
The study, published today (February 5, 2021) in Advances in science, trying to understand why neuroblastomas are in-depth, with some easy to treat and others with very low five-year survival rates. The fact that all neuroblastomas arise from sympathoblasts makes them attractive drug targets, since these cells are present only in the eardrum after the birth of the baby.
Neuroblastoma is a rare cancer that usually affects children under the age of five. It starts in the abdomen, usually in the adrenal glands – glands that produce hormones above the kidneys. Neuroblastoma is remarkable because its severity can vary between individuals. In some children, the cancer goes away untreated, but in others the cancer is useless. The five-year survival rate for neuroblastoma is one of the lowest in childhood cancers *.
This different view prompted the researchers to question whether the range of disturbance could be caused by neuroblastomas arising from different cell types at different stages of the child’s development in the womb. This was made possible by the emergence of a series of single-cell mRNAs, a high-resolution technology that identifies different cell types present in tissue according to the genes expressed by individual cells.
In this study, gene analysis of 19,723 cancer cells was examined and compared with a reference of 57,972 developmental adrenal cells in hopes of identifying the cell types from which neuroblastomas arise and finding novel treatment targets.
Dr Jan Molenaar, lead author of the study from the Princess Maxima Center for Pediatric Oncology in the Netherlands, said: “What is most surprising about our findings is that, despite the great diversity of clinical behaviors of neuroblastoma , that there is a broad neuroblastoma cell of a type found in all patients. Identifying sympathoblasts as the root of all neuroblastoma is an important step towards understanding how the disease develops and, hopefully, how we can treat it. “
Currently, many cancer treatments cause serious side effects for the patient. But in recent years, technological advances have encouraged drug development by allowing researchers to identify differences between the biological processes, such as expression of a particular gene, side by side. within healthy human cells and those within cancerous ones. These differences can be used to attack cancer cells without affecting the patient’s healthy cells.
The presence of sympathoblasts, a type of developmental cell not normally found in children after birth, makes it a promising drug target for the treatment of neuroblastoma.
Dr Karin Straathof, lead author of the study from Great Ormond Street Hospital, said: “Neuroblastoma is an uncommon cancer in that some tumors resolve without intervention, but nonetheless the disease remains at one of the lowest five-year survival rates of any childhood cancer. . This study fills important gaps in our knowledge of what neuroblastoma cells are and reveals novel treatment targets. My hope is that new, less invasive treatments can be developed by targeting sympathoblasts, a type of developmental cell that exists only in postmenopausal neuroblastoma tumors. was born. “
In addition to enabling the detection of sympathoblasts as a root of neuroblastoma, the single-cell reference map of the developing adrenal gland also contributes to the Human Atlas Cell ** project. The project aims to create complete reference maps of all types of human cells – the basic units of life – as a basis for understanding human health and the detection, monitoring, and treatment of diseases.
Dr Sam Behjati, lead author of the study from the Wellcome Sanger Institute and Cambridge University Hospitals, said: “Our study shows the power of looking at individual childhood cancer cells in revealing not -only one, but a combination of novel treatment ideas. raises the interesting expectation that a single-cell atlas of all types of pediatric tumors could transform our understanding of childhood cancer. “
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Contact information:
Dr. Matthew Midgley
Media Relations Office
Wellcome Sanger Institute
Cambridge, CB10 1SA
Phone: 01223 494856
Email: [email protected]
Notes to Editors:
* Further information on neuroblastoma is available from Cancer Research UK:
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** Further information on the Human Cell Atlas (HCA) project is available here:
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Published:
Gerda Kildisiute, Waleed M. Kholosy, Matthew D. Young et al. (2021). Tumors to normal single-cell mRNA comparisons reveal pan-neuroblastoma cancer cells. Advances in science. DOI: https: /
Funding:
This study was funded by Wellcome. Additional funding was received from the St Baldrick Foundation and the National Institute for Health Research (NIHR).
Selected Websites:
About the Princess Maxima Center
Every year around 600 babies are diagnosed with cancer in the Netherlands. One in four children with cancer still dies from the disease.
To treat children from cancer, all care and research in the Netherlands is based at the Princess Maxima Center for Pediatric Oncology in Utrecht. More than a decade ago, parents and healthcare professionals took the initiative. The new pediatric oncology center was opened by Queen Máxima of the Netherlands on 5 June 2018.
The mission of the Princess Maxima Center is to treat every child with cancer, with the best quality of life. The Princess Maxima 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 research at Great Ormond Street Hospital
Great Ormond Street Hospital is one of the leading children’s hospitals in the world with the widest range of specialist children’s healthcare specialists under one roof in the UK. The hospital’s innovative research and treatment offers hope to children from across the UK with the rarest, most complex and most often life-threatening conditions. All research by the Great Ormond Street Hospital NHS Foundation Trust and the UCL Great Ormond Street Institute of Child Health is made possible by the NIHR Great Ormond Street Hospital Biomedical Research Center.
Wellcome Sanger Institute
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