Written by | Guo Yuelong
High-grade gliomas in children progress rapidly and have a high fatality rate, with a five-year survival rate of only about 20% in children aged 0 to 14 years. Although the survival rate of infants and young children aged 0 to 4 years is much better than that of children over 5 years old, there is currently no clinical classification and treatment plan specifically for infants and young children aged 0 to 4 years.
Limited molecular biology data on patients aged 0 to 4 years with high-grade gliomas have limited research on this tumor molecular subtype; however, there have been multiple cases of gene fusion in clinical reports, suggesting that gene fusion may be one of the main causes of cancer in these infants and young children. If this extrapolation is correct, more targeted treatment can be offered to such patients.
In July 2020, Dr. Jones of the British ICR, together with many clinical and research teams from more than 70 medical institutions and research institutions around the world, published an Article High-Grade Gliomas Comprise Multiple Subgroups Characterized by Novel Targetable Gene in the AAR top journal Cancer Discovery Article by Fusions and Favorable Outcomes. The work conducted systematic molecular biology studies of patients with high-grade gliomas in infants and young children aged 0 to 4 years, and the results showed that about 50% of tumors were high-grade gliomas specific to this population, and these tumors contained gene mutations or gene fusions that could be used as drug targets. The study has the potential to provide better clinical typing and treatment options for high-grade gliomas in infants and young children.
Multiple clinical indicators (such as survival, prognosis, etc.) of high-grade gliomas in infants aged 0 to 4 years are different from those of children over 5 years of age, indicating that existing histopathological grades may not accurately reflect the biology of tumors, so the researchers collected 241 cases under 4 years of age and performed systematic histological grading, methylation analysis, and gene chip, whole genome or exome sequencing.
Of the 241 samples, the researchers identified 130 tumor samples specific to the infant population after excluding tumors of known molecular subtypes by methylation analysis. Further molecular biology studies have been conducted on tumors specific to these infant populations.
Enrollment Criteria and Molecular Marker Research Process
The researchers found new subtypes in infants and young children under the age of 4 with high-grade gliomas, and a significant proportion of these patients had gene fusions of ALK, NTRK1/2/3, ROS1, or MET that could be targeted as drugs. The location and frequency of gene mutations and gene fusion in patients are described in detail.
Schematic diagram of the classification of high-grade gliomas in infants and young children
It is worth mentioning that the researchers used a human mouse model to further test tumor samples containing gene fusion. The results showed that targeted drugs had good efficacy against tumors containing gene fusion, at least in human-derived mouse models. For several patients who are willing to receive targeted drug therapy in the clinic, the prognosis is also more optimistic.
Figure 3.Targeted therapy results of tumor samples containing ALK fusion gene mutations in human mice
The study provides the largest and most comprehensive molecular biological data of infant glioma, proposes a new classification system, and lays a solid foundation for updating and improving the clinical treatment of infant glioma.
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