Medical Student Department of Neurosurgery, Brigham and Women's Hospital Brookline, MA, US
Introduction: Meningiomas have a complex genome, with copy number alterations and DNA methylation signatures associating with recurrence and response to therapy. Structural variants (SV), such as translocations, are additional genomic alterations implicated in cancer subtypes. Capturing the breadth of SVs and characterizing their prognostic potential has proved difficult for meningioma. We sought to assess a novel profiling technology previously applied to liquid cancers, optical genome mapping (OGM), to survey the entire genomic architecture of meningioma.
Methods: Ultra-high molecular weight DNA was extracted from frozen meningioma samples collected after surgical resection. Labeled DNA strands were imaged to detect SVs, including blind spot events such as balanced translocations which are not otherwise detected by other profiling methods. SVs and copy number alterations captured by OGM were compared against whole-genome microarray profiling.
Results: We profiled 27 meningiomas (14 WHO grade 1, 10 WHO grade 2, 3 WHO grade 3) for whole-genome SVs using OGM. A majority of meningiomas (70.4%) had at least one translocation or fusion event, with 51.9% of genomes having an SV linked to a copy number alteration, such as an event between chromosome 10p and 22q resulting in the loss of both arms. Specific chromosome arms were enriched for this phenomenon, particularly chromosome 1p: 56.3% of loss events on 1p were associated with an SV while the rest occurred without a structural rearrangement. Though radiation-induced meningiomas had a greater frequency of translocation events (median: 5, range: 1-25) compared to sporadic tumors (median: 1, range: 0-61), they were not uniform. Only 2 of 6 radiation-induced meningiomas showed large-scale chromothripsis rearrangements.
Conclusion : OGM reveals a spectrum of SVs in meningioma as well as a distinct mode of copy number alterations associated with SVs, potentially holding insight into biological mechanisms of tumor development. Successful profiling of meningiomas demonstrates proof-of-concept for solid tumor mapping.
.jpg)
