In-person Flash Talk & E-Poster Presentation 34th Lorne Cancer Conference 2022

The molecular profile of secondary meningiomas in survivors of childhood non-central nervous system cancers (#14)

Catherine Corriveau-Bourque 1 , Derek Wong 2 , Frank van Landeghem 3 , Matija Snuderl 4 , Maria Spavor 1 , Stephen Yip 5 , David D Eisenstat 6 7
  1. Pediatrics, University of Alberta, Edmonton, Alberta, Canada
  2. Cancer Genomics Program, Princess Margaret Cancer Centre, University Health Network, Toronto, Ontario, Canada
  3. Laboratory Medicine and Pathology, University of Alberta Hospital, Edmonton, Alberta, Canada
  4. Pathology, New York University, New York, NY, USA
  5. Pathology, BC Cancer, Vancouver, BC, Canada
  6. The Royal Children's Hospital Melbourne, Parkville, VIC, Australia
  7. Neuro-Oncology Laboratory, Murdoch Children's Research Institute, Parkville, Victoria, Australia

INTRODUCTION: Cranial irradiation remains part of the management of some childhood malignancies and secondary meningiomas have been recognized as a late effect of this therapy. Secondary meningiomas have been reported in patients who received low and high dose cranial irradiation. They arise on average 20 years post exposure to cranial irradiation. The molecular and genetic profile of primary meningiomas has been well studied; however, there are only a few studies describing these in radiation-induced meningiomas (RIM).

METHODS: We identified patients followed at the Childhood Cancer Survivor Clinic, Stollery Children’s Hospital, Edmonton, Canada who had a history of non-central nervous system malignancies and received cranial irradiation and who developed meningiomas between the clinic inception in 1971 and 2013. Whole exome sequencing (WES), RNA sequencing (RNAseq) as well as epigenomic DNA methylation profiling were performed for patients where meningioma tumor tissue and germline DNA were available.

RESULTS: Of the 96 patients having received cranial irradiation, 16 (16.7%) developed symptomatic meningiomas. This patient cohort is unique; all 16 patients identified received 2000-2400 cGy of cranial irradiation. No patients who received <2000cGy of cranial irradiation developed meningiomas, suggesting a threshold dose. 9/16 (56%) had WHO Grade 2 meningiomas or greater and 7/16 (44%) of meningiomas infiltrated other tissues. Post-surgical recurrences occurred in 43%. Patients experienced considerable morbidities directly attributable to the meningiomas or their treatment. 14 patients had samples suitable for further analysis. NF2 mutations were the most common (7; 4 DNA, 3 fusion). Other meningioma related genes with mutations identified in our patient cohort include: TRAF7, SMARCA2 (2), AKT3 (2), POLQ, TET1, BRCA2, CHECK2, and MLH3. Copy number alternations were noted with increased frequency on chromosomes 1p, 22q, and 19q. 850k methylation analysis with PCA as well as UMAP and tSNE did not conclusively show any clustering. Ongoing additional studies include examining tumor mutation burden and the radiation mutational profile.

CONCLUSIONS: This study examined the RIM in a cohort of patients having received similar doses of radiation for their childhood cancer. There is increased risk of radiation-induced meningioma in survivors of non-CNS cancers given ≥ 2000 cGy during childhood. To date, our findings are consistent with previously described primary and RIM mutations. Enhanced knowledge in secondary meningiomas is crucial for accurate patient counselling, prognostication, and treatment.