BRAF alteration status and the histone H3F3A gene K27M mutation segregate spinal cord astrocytoma histology

Excerpt

Intramedullary spinal cord neoplasms represent 2–4 % of central nervous system tumors, of which astrocytic gliomas represent 80 %. Patients presenting with spinal cord astrocytomas span the traditional pediatric and adult age divisions, having an overall age-distribution that is younger than cohorts with supratentorial gliomas. WHO grade I and II astrocytomas have better outcomes that are largely dependent on extent of surgical resection [10], whereas Grade III and IV astrocytomas are less amenable to safe surgical resection, and typically require adjuvant radiation and chemotherapy for treatment. Given the premium on preserving neurologic function during spinal cord surgery, intraoperative frozen section histologic analysis has an important role in driving therapeutic decision-making. However, histologic grading can be challenging in spinal cord astrocytomas because of the often relatively small samples obtained at the time of the surgical procedure. Therefore, grade-defining molecular biomarkers would be particularly useful for the accurate diagnostic classification of these tumors [13]. Recent genome level sequencing studies of supratentorial gliomas revealed discrete genomic alterations that discriminate pilocytic astrocytomas, WHO grade II and III diffuse gliomas, and WHO grade IV glioblastoma (GBM), with notable differences between pediatric [9, 14, 15, 20] and adult [2, 3, 6] patients. To address the hypothesis that genomic alterations could segregate spinal cord astrocytoma histologic grades, we performed sequencing of cancer-related genes in a cohort of 17 tumors. …