Deciphering the structural complexities of pediatric low grade gliomas
Cancer Genetics and Therapeutics
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Primary Categories:
- Cancer
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Secondary Categories:
- Cancer
Introduction:
Despite the relatively high success rate of treatment in pediatric patients with low grade gliomas (LGGs), some children have LGGs that behave more aggressively, leading to multiple recurrences, metastasis, and/or death. The reason for this discrepancy is not fully understood but may be due to the underlying differences in genomic composition. Limitations of short-read sequencing in structural variant (SV) identification present gaps in our understanding of variants that may influence tumor behavior and treatment response.
Methods:
Here, we used optical genome mapping (OGM) to detect structural variants in 10 aggressive (postmortem, metastatic, or recurrent following standard of care therapy) and 10 non-aggressive (surgery alone) LGG samples.
Results:
The initial sample processing and analysis focused on samples for which KIAA1549::BRAF fusion was identified previously and samples for which the fusion was not present. OGM analysis successfully identified the KIAA1549::BRAF fusion in LGG samples with varying number of variant allele fraction (VAF) supporting that LGG patients have different degrees of cell compositions carrying the KIAA1549::BRAF fusion. Further stratification of samples based on aggressive vs non-aggressive tumor behavior showed that aggressive tumors contain more SVs, including large chromosomal aberrations, than their non-aggressive counterparts.
Conclusion:
Our preliminary data demonstrate that the application of OGM in metastatic, refractory, and recurrent pediatric LGGs to define SV patterns could elucidate novel mechanisms involved in tumor behavior.
Despite the relatively high success rate of treatment in pediatric patients with low grade gliomas (LGGs), some children have LGGs that behave more aggressively, leading to multiple recurrences, metastasis, and/or death. The reason for this discrepancy is not fully understood but may be due to the underlying differences in genomic composition. Limitations of short-read sequencing in structural variant (SV) identification present gaps in our understanding of variants that may influence tumor behavior and treatment response.
Methods:
Here, we used optical genome mapping (OGM) to detect structural variants in 10 aggressive (postmortem, metastatic, or recurrent following standard of care therapy) and 10 non-aggressive (surgery alone) LGG samples.
Results:
The initial sample processing and analysis focused on samples for which KIAA1549::BRAF fusion was identified previously and samples for which the fusion was not present. OGM analysis successfully identified the KIAA1549::BRAF fusion in LGG samples with varying number of variant allele fraction (VAF) supporting that LGG patients have different degrees of cell compositions carrying the KIAA1549::BRAF fusion. Further stratification of samples based on aggressive vs non-aggressive tumor behavior showed that aggressive tumors contain more SVs, including large chromosomal aberrations, than their non-aggressive counterparts.
Conclusion:
Our preliminary data demonstrate that the application of OGM in metastatic, refractory, and recurrent pediatric LGGs to define SV patterns could elucidate novel mechanisms involved in tumor behavior.