Zeitschrift für Morphologie und Anatomie

Why primary tumours/malignancies of the nerve cells are so rare?

Abstract

Eliza Roche

Introduction: Primary tumours associated with nerve cells are exceptionally rare whereupon the majority of these tumours present as benign. Neurons develop oncogenic mutations less than their supporting neuroglias which are transformed into glioma tumours.

Methods and materials: Using a multi-faceted approach, search strategies were generated using specific keywords and performed on selected scientific databases. Literature searches were performed and a shortlist of seven publications was generated following a strict criteria based selection process.

Results: Reduced number of proliferating cells: Early cell cycle exit results in the inability for nerve cells to regenerate as well as preventing malignancies from developing as no DNA is required to replicate. Additionally, post-mitotic Neurons have the ability to re-enter the cell cycle without producing two daughter cells to repair damaged DNA.

Tumour suppressor proteins: A high abundancy of PTEN and TP53 are present in the CNS and PNS (higher than most other areas of the body). These act as protective mechanisms for detection of damaged DNA to mark cells for immediate apoptosis.

Inhospitable environment created by the lymphatic system: An extensive network of lymphatic vessels channel tumour cell dissemination to cervical lymph nodes. This stimulates immune responses by the high abundancy of dendritic cells and the destruction of tumour cells.

Immunity in the nervous system: Natural Killer (NK) cells, seen in high abundancy in the CNS, are the most effective response factors against tumours and viral infections. NK cells express a large range of cellular receptors to tumour ligands which stimulates NK mediated cytotoxicity.

Hereditary: Li-Fraumeni syndrome, Cowden syndrome and neurofibromatosis 1 syndrome represent three genetic conditions with associated high risks of developing tumors such as glioblastoma, schwannoma and astrocytoma.

Geographic location: There is a correlation between countries with high Human Development Index (HDI) and the incidence and mortality of brain tumors.

Conclusions and future directions: Mutations are rare in nerve cells due to their inability to proliferate and regenerate. Mutated nerve cells are marked for DNA damage repair or apoptosis preventing passing on of oncogenic mutations. The high abundancy and range of immune cells surveilling the nervous system and lymphatic system mark cancerous growths for degradation. Germline mutations account for a small proportion of nerve cell tumors.