Genomic Landscape of Intramedullary Spinal Cord Gliomas

Abstract

Intramedullary spinal cord tumors (IMSCTs) are rare neoplasms that have limited treatment options and are associated with high rates of morbidity and mortality. To better understand the genetic basis of these tumors we performed whole exome sequencing on 45 tumors and matched germline DNA, including twenty-nine spinal cord ependymomas and sixteen astrocytomas. Though recurrent somatic mutations in IMSCTs were rare, we identified NF2 mutations in 15.7% of tumors (ependymoma, N = 7; astrocytoma, N = 1), RP1 mutations in 5.9% of tumors (ependymoma, N = 3), and ESX1 mutations in 5.9% of tumors (ependymoma, N = 3). We further identified copy number amplifications in CTU1 in 25% of myxopapillary ependymomas. Given the paucity of somatic driver mutations, we further performed whole-genome sequencing of 12 tumors (ependymoma, N = 9; astrocytoma, N = 3). Overall, we observed that IMSCTs with intracranial histologic counterparts (e.g. glioblastoma) did not harbor the canonical mutations associated with their intracranial counterparts. Our findings suggest that the origin of IMSCTs may be distinct from tumors arising within other compartments of the central nervous system and provides the framework to begin more biologically based therapeutic strategies.

Comprehensive analysis of the functions and prognostic significance of RNA-binding proteins in bladder urothelial carcinoma

“…ELP3 and CTU1/2, partner enzymes in uridine 34(U34) mcm 5 s 2 -tRNA modi cation, are upregulated and promote metastasis in human breast cancers [38]. CTU1 copy number ampli cations were identi ed in 25% of myxopapillary ependymomas [39]. Qin et al had demonstrated DARS2 as a hepatocarcinoma gene that could promote the progression of hepatocarcinoma cell cycle and inhibit the apoptosis of hepatocarcinoma cells [40].…”

Identification and Validation of RNA Binding Protein-associated Prognostic Model for Neuroblastoma

“…The related pathways include gene expression and tRNA processing, and its function is related to tRNA binding and nucleotide transferase activity. CTU1 promotes cancer resistance to targeted therapy [30], related to Spinal Cord Gliomas' high rates of morbidity and mortality [31], and up-regulation of CTU1 is involved in human breast cancer metastasis.…”

Surgical treatment and neurological outcome of infiltrating intramedullary astrocytoma WHO II–IV: a multicenter retrospective case series

“…Interestingly, IDH-1 could not be identified in any of the high-grade tumor specimens, which is congruent with the current literature [39], suggesting that glioblastoma of the spinal cord may correspond only to primary high-grade glioma. In a recent study investigating the genetic profile of intramedullary astrocytomas, Zhang et al postulated that astrocytomas of the spinal cord may arise from alternative mechanisms of tumorigenesis compared to intracranial astrocytomas [40]. Due to their possibly distinct genetic profile and nonconformity with their intracranial counterparts, genetic alterations should be discussed for targeted therapy, regarding the limited prognosis of patients with spinal infiltrating astrocytomas with current treatment strategies [40][41][42].…”

“…In a recent study investigating the genetic profile of intramedullary astrocytomas, Zhang et al postulated that astrocytomas of the spinal cord may arise from alternative mechanisms of tumorigenesis compared to intracranial astrocytomas [40]. Due to their possibly distinct genetic profile and nonconformity with their intracranial counterparts, genetic alterations should be discussed for targeted therapy, regarding the limited prognosis of patients with spinal infiltrating astrocytomas with current treatment strategies [40][41][42]. Further molecular analysis is needed for evaluation of tumor origin and possible therapeutic agents [42], as neuropathological diagnostics evolve and may open further diagnostics paths for molecular characterization in small tumor samples.…”