Molecular profiling obtains information of clinicopathological features of meningioma

Abstract

Meningioma is the most common tumour of central nervous system in adults which originates from intracranial meningothelial arachnoid cap cells. Most meningiomas are small incidental findings but larger ones are often detected after patient´s observations of gradually increasing intracranial pressure which often causes headaches and seizures. The majority of meningiomas (about 80%) can be removed surgically. If the achieved surgical resection is incomplete or unfeasible, stereotactic radiosurgery (SRS) and fractioned radiotherapy (FRT) are also alternative treatment options. Moreover, even when complete surgical removal (i.e. extirpation) of the tumour is achieved, ∼20% of patients have an aggressive recurring or progressing tumour, which causes morbidity and even mortality, and may require retreatment.

Meningiomas have heterogenetic morphology and the World Health Organization (WHO) classifies these tumours according to severity to three grade and further to 15 diverse subtypes. This classification went through significant changes in 2016, when WHO instructed inclusion of molecular pathology into the definition of tumour entities. The purpose of this improvement is to increase the level of objectivity in brain tumour diagnostics. The revised WHO 2016 CNS classification categorizes 9 meningioma variants as benign grade I tumours while 3 variants are categorized as more aggressively growing grade II meningiomas (so called atypical meningiomas) and 3 other aggressively and invasively growing variants as grade III meningiomas (so called malignant meningiomas).

This bachelor thesis is a literature review which concerns results of performed molecular profiling of meningioma made by next generation sequencing from three different viewpoints. Arachnoid cap cells seem to harbour certain causative mutations which have a clear effect on clinicopathological features e.g. localization and can predict progression of developing meningioma. Results of accomplished literature review are presented in three tables. The first table shows association between these specific recurrent mutated genes and histological subtype of meningioma listed by WHO grades. The second table presents founded results of association between anatomical position and repetitive mutations in meningioma. The main result in general was the location of histopathologically benign grade I tumours in the anterior or medial cranial base whereas meningiomas graded as II or III seem to develop in convexities. This thesis also concerns less studied subject compared to above presented topics: the effect on the recurrent gene mutations in meningiomas to the progression free survival (PFS) and overall survival (OS) of patients. Consequently, the third graph demonstrates the effect of mutated NF2, DMD and TERT genes to the PFS and OS of patients presented by Kaplan–Meier estimates.

Even though almost all histological subtypes of meningioma harbour known specific mutations, so far unrecognizable alterations are discovered from 5 % of evaluated meningiomas. The clarification of their status is necessary to enable extensive and informative profiling of meningiomas. Therefore, the main ambition of current studies is the development of personalized medicines according to genotype of meningiomas. This is potentially conceivable even in near future, thanks to results from performed molecular profiling of meningioma which main findings are presented in this thesis.