Unlocking the Secrets of Childhood Cancer Genetics

Scientists have revealed a fresh insight into the genetic pathway of childhood cancer, providing new potential for personalized treatment.

Researchers at the University of Sheffield have developed a stem cell model to examine the origins of neuroblastoma, a cancer that usually affects newborns and young children.

Neuroblastoma is the most frequent childhood tumor that develops from immature nerve cells found in several areas of the body claiming the lives of roughly 600 children in the European Union and the United Kingdom each year.

Until now, inadequate laboratory techniques have made it difficult to investigate genetic changes and their involvement in the onset of neuroblastoma. The formation of early neuroblastoma cancer-like cells is replicated in a novel model created by researchers at the University of Sheffield in partnership with the St Anna Children’s Cancer Research Institute in Vienna. This model provides insight into the genetic mechanism of the disease.

The study, published in Nature Communications, provides insight into the complex genetic pathways that give rise to neuroblastoma. The international research team discovered that certain mutations in chromosomes 17 and 1, as well as overactivation of the MYCN gene, significantly influence the formation of aggressive neuroblastoma tumors.

Childhood cancer is frequently identified and found late, leaving researchers with limited understanding of the settings that contribute to tumor initiation, which happens very early in fetal development. Models that mimic the circumstances that cause cancer to form are critical for understanding tumor initiation.

Neuroblastoma often develops in the womb when a group of normal embryonic cells known as ‘trunk neural crest (NC)’ become altered and malignant.

The new study, led by stem cell expert Dr. Ingrid Saldana of the University of Sheffield’s School of Biosciences and computational biologist Dr. Luis Montano of the St Anna Children’s Cancer Research Institute in Vienna, discovered a way to use human stem cells to grow trunk NC cells in a petri dish.

These cells have genetic modifications frequently observed in aggressive neuroblastoma tumors. Through the use of cutting-edge imaging methods and genomics analysis, the researchers discovered that the altered cells began to behave like cancer cells and bore a striking resemblance to the neuroblastoma cells present in sick children.

The results provide fresh hope for the development of specialized therapies that target the disease precisely while reducing the side effects that patients now endure from current treatments.

Our stem cell-based model mimics the early stages of aggressive neuroblastoma formation, providing invaluable insights into the genetic drivers of this devastating childhood cancer. By recreating the conditions that lead to tumour initiation, we will be able to understand better the mechanisms underpinning this process and thus design improved treatment strategies in the longer term.

Dr Anestis Tsakiridis, Study Lead Author and Group Leader & Lecturer, University of Sheffield

Dr Tsakiridis added, “This is very important as survival rates for children with aggressive neuroblastoma are poor and most survivors suffer from side effects linked to the harsh treatments currently used, which include potential hearing, fertility, and lung problems.

Dr Florian Halbritter, from St. Anna Children's Cancer Research Institute and the study's second lead author, stated, “This was an impressive team effort, breaching geographic and disciplinary boundaries to enable new discoveries in childhood cancer research.

The University of Sheffield’s cancer research strategy is supported by this study. The University hopes to reduce the number of fatalities caused by cancer by doing high-quality research that will result in enhanced treatments and methods to better identify and prevent cancer while also enhancing quality of life.

Source:
Journal reference:

Saldana-Guerrero, I. M., et al. (2024) A human neural crest model reveals the developmental impact of neuroblastoma-associated chromosomal aberrations. Nature Communications. doi.org/10.1038/s41467-024-47945-7

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