Scott Ryall1, Miguel Guzman2, Samer K Elbabaa3, Betty Luu4, Stephen C Mack5, Michal Zapotocky6, Michael D Taylor1,4,7, Cynthia Hawkins1,4,8, Vijay Ramaswamy9,10. 1. Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, ON, Canada. 2. Pathology and Laboratory Medicine, Cardinal Glennon Children's Hospital, Pathology Department, Saint Louis University, Saint Louis, MO, USA. 3. Department of Neurological Surgery, Saint Louis University School of Medicine, Saint Louis, MO, USA. 4. Program in Developmental and Stem Cell Biology, Arthur and Sonia Labatt Brain Tumour Research Centre, Hospital for Sick Children, Toronto, ON, Canada. 5. Cleveland Clinic Foundation, Cleveland, OH, USA. 6. Division of Haematology/Oncology, Hospital for Sick Children, University of Toronto, 555 University Ave, Toronto, ON, M5G 1X8, Canada. 7. Division of Neurosurgery, Hospital for Sick Children, Toronto, ON, Canada. 8. Department of Pediatric Laboratory Medicine, Hospital for Sick Children, Toronto, ON, Canada. 9. Division of Haematology/Oncology, Hospital for Sick Children, University of Toronto, 555 University Ave, Toronto, ON, M5G 1X8, Canada. vijay.ramaswamy@sickkids.ca. 10. Program in Neuroscience and Mental Health, Arthur and Sonia Labatt Brain Tumour Reserch Centre, Hospital for Sick Children, Toronto, ON, Canada. vijay.ramaswamy@sickkids.ca.
Abstract
BACKGROUND: Mutations in the tail of histone H3 (K27M) are frequently found in pediatric midline high-grade glioma's but have rarely been reported in other malignancies. Recently, recurrent somatic nucleotide variants in histone H3 (H3 K27M) have been reported in group A posterior fossa ependymoma (EPN_PFA), an entity previously described to have no recurrent mutations. However, the true incidence of H3 K27M mutations in EPN_PFA is unknown. METHODS: In order to discern the frequency of K27M mutations in histone H3 in EPN_PFA, we analyzed 151 EPN_PFA previously profiled with genome-wide methylation arrays using a validated droplet digital PCR assay. RESULTS: We identified only 1 case out of 151 EPN_PFA harboring the K27M mutation indicating that histone mutations are extremely rare in EPN_PFA. Morphologically, this single mutated case is clearly consistent with an ependymoma, and the presence of the K27M mutation was confirmed using immunohistochemistry. DISCUSSION: K27M mutations are extremely rare in EPN_PFA. Routine evaluation of K27M mutations in EPN_PFA is of limited utility, and is unlikely to have any bearing on prognosis and/or future risk stratification.
BACKGROUND: Mutations in the tail of histone H3 (K27M) are frequently found in pediatric midline high-grade glioma's but have rarely been reported in other malignancies. Recently, recurrent somatic nucleotide variants in histone H3 (H3 K27M) have been reported in group A posterior fossa ependymoma (EPN_PFA), an entity previously described to have no recurrent mutations. However, the true incidence of H3 K27M mutations in EPN_PFA is unknown. METHODS: In order to discern the frequency of K27M mutations in histone H3 in EPN_PFA, we analyzed 151 EPN_PFA previously profiled with genome-wide methylation arrays using a validated droplet digital PCR assay. RESULTS: We identified only 1 case out of 151 EPN_PFA harboring the K27M mutation indicating that histone mutations are extremely rare in EPN_PFA. Morphologically, this single mutated case is clearly consistent with an ependymoma, and the presence of the K27M mutation was confirmed using immunohistochemistry. DISCUSSION: K27M mutations are extremely rare in EPN_PFA. Routine evaluation of K27M mutations in EPN_PFA is of limited utility, and is unlikely to have any bearing on prognosis and/or future risk stratification.
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