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Published on: September 13, 2022
Molecular Profiling of Pediatric and Adult Glioblastoma
Catherine K Gestrich1, Audrey N Jajosky1, Robin Elliott1
1Department of Pathology, University Hospitals Cleveland Medical Center, Cleveland, OH.
Insights
Pediatric glioblastoma (GBM) shows distinct molecular differences from adult GBM, with a higher frequency of mismatch repair gene alterations. These findings suggest potential benefits from immune checkpoint inhibitors for young patients.
Area of Science:
- Neuro-oncology
- Pediatric oncology
- Molecular pathology
Background:
- Glioblastoma (GBM) is a rare but fatal pediatric central nervous system neoplasm.
- Pediatric GBM exhibits distinct molecular profiles compared to adult GBM.
- Some pediatric GBMs are linked to cancer predisposition syndromes like constitutional mismatch repair deficiency (CMMRD).
Purpose of the Study:
- To characterize the molecular profiles of pediatric and adult GBM.
- To investigate differences in genetic alterations between pediatric and adult GBM cohorts.
- To assess the potential of immune checkpoint inhibitors in pediatric GBM based on molecular findings.
Main Methods:
- Next-generation sequencing (NGS) was employed.
- Immunohistochemistry (IHC) for mismatch repair proteins was performed.
- A cohort of 11 pediatric and 11 adult GBMs was analyzed.
Main Results:
- Pediatric GBMs exhibited a higher number of genetic alterations than adult GBMs.
- A higher frequency of alterations in mismatch repair genes was observed in pediatric GBM.
- One pediatric patient with CMMRD syndrome was identified.
Conclusions:
- Pediatric and adult GBM have distinct molecular characteristics.
- Pediatric GBM frequently shows alterations in mismatch repair genes, indicating potential susceptibility to immune checkpoint inhibitors.
- Routine IHC for mismatch repair alterations is recommended for all pediatric GBM cases.
Objectives:
Although glioblastoma (GBM) is rare in the pediatric population, it is the most common cause of death among children with central nervous system neoplasms. Recent molecular profiling of these neoplasms has demonstrated distinct differences in comparison to their adult counterparts. Moreover, many pediatric GBMs occur within the context of cancer predisposition syndromes, such as constitutional mismatch repair deficiency syndrome (CMMRD). Children with CMMRD who develop GBM exhibit a high tumor mutational burden and may benefit from treatment with immune checkpoint inhibitors.
Methods:
We performed next-generation sequencing and immunohistochemistry for mismatch repair proteins in our cohort of pediatric and adult GBMs to further characterize the molecular profiles of these groups.
Results:
We examined a total of 11 pediatric and 11 adult GBMs. Pediatric patients had a higher number of alterations compared to their adult counterparts. They also had a higher frequency of alterations in the mismatch repair genes, which can be detected by immunohistochemistry (IHC). We also identified one pediatric patient with CMMRD syndrome.
Conclusions:
Our study highlighted the distinct molecular differences between pediatric and adult GBM. We also demonstrated that pediatric patients have a higher frequency of alterations in the mismatch repair genes, which may render them susceptible to treatment with immune checkpoint inhibitors. These alterations can be detected using routine IHC and should be performed on all pediatric GBM.
