Molecular Biomarkers of Brain and Spinal Cord Astrocytomas

Abstract

Spinal cord astrocytomas are rare diseases of the central nervous system. The localization of these tumors and their infiltrative growth complicate their surgical resection, increase the risk of postoperative complications, and require more careful use of radio- and chemotherapy. The information on the genetic mutations associated with the onset and development of astrocytomas provides a more accurate neoplasm diagnosis and classification. In some cases, it also allows one to determine the optimal methods for treating the neoplasm, as well as to predict the treatment outcomes and the risks of relapse. To date, a number of molecular markers that are associated with brain astrocytomas and possess prognostic value have been identified and described. Due to the significantly lower incidence of spinal cord astrocytomas, the data on similar markers are much more sparse and are presented with a lesser degree of systematization. However, due to the retrospective studies of clinical material that have been actively conducted abroad in recent years, the formation of statistically significant genetic landscapes for various types of tumors, including intradural spinal cord tumors, has begun. In this regard, the purpose of this review is to analyze and systematize the information on the most significant genetic mutations associated with various types of astrocytomas, as well as discuss the prospects for using the corresponding molecular markers for diagnostic and prognostic purposes.

Diffuse midline glioma with H3 K27M mutation of the spinal cord: A series of 33 cases

“…According to the reviewed literature, p53 positivity is common in DMGSCs (20-50%) 5,16 and WHO III-IV spinal cord astrocytomas (60-67%). 32 The co-occurrence of the H3 K27M and TP53 mutations in gliomas had a trend of poorer prognosis (13.5 ± 2.3 months) compared to that of gliomas without TP53 mutation (20.0 ± 3.85 months) but had no significant effect on survival period. Some authors postulate that the H3 K27M mutation is a key driver mutation, and that the tumor suppressor gene product p53 positivity, indicative of a loss-of function mutation, plays an essential role in tumor development in both pediatric and adult spinal cord high-grade gliomas.…”

The Search for Molecular Markers in a Gene-Orphan Case Study of a Pediatric Spinal Cord Pilocytic Astrocytoma

“…Notably, in the described study, no specimen in the cohort displayed the BRAFV600E mutation. A very recent survey of the literature data reported that the main genetic variations associated with spinal cord astrocytomas involved BRAF-KIAA1549 fusions in about 32% of cases, and TP53 mutations in 60-67% of WHO grades III-IV spinal cord astrocytomas (27). Generally, it was also established that the molecular profile of astrocytomas in children differ significantly from the adult variants and mainly contain mutations in BRAF, H3F3A and ATRX genes.…”

“…Generally, it was also established that the molecular profile of astrocytomas in children differ significantly from the adult variants and mainly contain mutations in BRAF, H3F3A and ATRX genes. However, to date, there is no information on the identification of specific spinal cord astrocytomas markers such IDH1/2, H3F3A and FGFR2 related to brain glial tumors (27).…”

MiR-92a-3p promote s invasion and migration of hepatocellular carcinoma cells by targeting PTEN

“…Phosphatase PTEN is involved in the dephosphorylation of membrane-bound phosphatidylserine PIP3 to PIP2, and thus regulates the PKB/AKT signaling pathway (22). In addition, PTEN is reported to play a main role in negatively regulating the PI3K/AKT pathway and inhibit PTEN-regulated apoptosis (23).…”