Researchers have discovered new variations in neuroblastoma that may result in a more precise prognosis and more targeted treatments for this devastating childhood cancer. The study has uncovered three new subgroups of the most common type of neuroblastoma, each with different genetic traits, expected outcomes, and distinguishing features. These findings provide valuable insights into which treatments may be the most effective.Published in the British Journal of Cancer, a study has identified three new subgroups of the most common type of neuroblastoma. Each subgroup has different genetic traits, expected outcomes, and distinguishing features that provide insight into which treatments may be most effective.
Dr Yihua Wang from the University of Southampton, a senior author on the paper, stated: “This research is a significant advancement in our understanding of MYCN non-amplified neuroblastomas. The findings are remarkable. These neuroblastomas can be categorized into three distinct subgroups, each with unique prognostic implications and varying vulnerabilities.
There are few treatment options available for neuroblastoma, making it challenging for healthcare professionals to find an effective therapy for the disease.
Every year, approximately 100 children in the UK are diagnosed with neuroblastoma, accounting for a small percentage of all childhood cancers. Neuroblastoma originates in nerve cells called neuroblasts and can manifest in various parts of the body, such as the abdomen, chest, neck, or pelvis, and has the potential to spread to other areas.
The overall prognosis for neuroblastoma is discouraging, with only 20% of patients surviving 5 years after being diagnosed. The chances of curing the cancer vary greatly, as some tumors may regress on their own while others are resilient to treatment and continue to progress.
Scientists at the University of Southampton and China conducted a study to investigate the significance of the amplification of the MYCN gene in neuroblastomas. This gene amplification is present in about 20% of cases and is responsible for approximately 40% of high-risk neuroblastomas. The researchers aimed to gain a better understanding of cases where the MYCN gene is not amplified in order to comprehend the variations in outcomes within this subgroup. They analyzed more than 1,500 biopsy samples from 16 different datasets obtained from Gene Expression Omnibus (GEO) and ArrayExpress using advanced analytical techniques.
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The team has identified three distinct subtypes of MYCN non-amplified cases based on their transcriptional signatures. These transcriptional signatures are patterns of gene expression that can provide valuable insights into biological processes.
The first subgroup makes up about half of MYCN non-amplified cases and has the best prognosis. They have a long-term survival rate of over 85%, despite some cases being clinically classified as high risk.
Subgroup 2, which represents a quarter of MYCN non-amplified cases, had the worst outcomes with a long-term survival rate of 50%. Interestingly, this group had a similar genetic signature to a previously identified aggressive neuroblastoma subtype.
The “inflamed” gene signature is the hallmark of Subgroup 3, comprising a quarter of MYCN non-amplified cases. This subgroup shows significantly higher levels of activity in immune cells. Researchers also found that patients in this subgroup were detected. This finding suggests that patients in this subgroup may benefit from treatment with AURKA inhibitors.It is expected that patients with MYCN non-amplified neuroblastomas will have a better response to immunotherapy, according to Dr. Wang. This research allows for more personalized medicine in the treatment of neuroblastomas by using transcriptional subtyping. This can lead to more accurate prognosis and tailored therapies, potentially improving outcomes and quality of life for patients. The project received support from the UK Medical Research Council and the Natural Science Foundation of China.
