**Author details**

**6. Possible relationships between location and genetic signature in primary**

A unique finding is that the location of certain primary brain tumors determines their genetic characteristics. Cranial base meningiomas are less malignant compared to the non-cranial base meningiomas [85]. The frequencies of grade II and III cranial base and non-cranial base meningiomas are 3.5 and 12.1%, respectively. These findings origin from a clinical-patholog‐ ical observation. The biological, molecular, and genetic basis of this fact requires further explanation. A simple answer would be the diverse embryological origins of the dura mater in various locations of human skull [86]. A recently published paper showed (utmost) intriguing data about meningioma biology, which is going to help our understanding of this tumor, of which 85–90% is classified as benign (grade I), but has in certain locations an aggressive course. Meningiomas regarding their genetic origin are divided as NF2 and non-NF2 meningiomas. The non-NF2 meningiomas behave clinically different and are generally always benign, with chromosomal stability, and originate from the medial skull base. In contrastto these findings, meningiomas with mutant NF2 and/or chromosome 22 loss are more likely to be atypical and demonstrate genomic instability and are localized to the cerebral and cerebellar hemispheres. This group concludes their study: "Collectively, these findings identify distinct meningioma subtypes, suggesting avenues for targeted therapeutics" [87]. There is a mutational profile of a meningioma, which can be predicted based on its anatomi‐ cal location in human calvarium. This finding may provide a unique treatment strategy for midline tumors, which may have a response to medical treatment like hedgehog inhibitors. There are treatment-resistant meningiomas, which are surgically unresectable, recurrent, or invasive. In these patients one can reserve surgery or irradiation, bearing in mind that there is an independent risk factor for progression of these generally benign considered primary brain tumors. This location-based molecular and genetic data provides an updated information about prognosis and treatment response of meningiomas. This update research, which is collected over 300 meningiomas, is a valuable finding, regarding designing personalized

Another fact about meningioma is that there is a subgroup of meningiomas, which are histopathologically classified as grade I meningioma, but recurs during follow-up in a short distance unexpectedly as grade II and later as grade III meningiomas. Although the malig‐ nant progression of gliomas is considerably well defined and researched entity, there is lack of scientific data about meningiomas, regarding which one is going to transform malignant‐ ly. Al-Mefty et al. explained this clinical observation with their FISH analysis of primary and recurring meningiomas with malignant progression in their series. They studied 175 recur‐ rent meningiomas and found that 11 tumors showed histopathologically verified progres‐ sion to a higher grade. In this study, the cytogenetic analysis with FISH showed deletions of 22, 1p, and 14q. The interesting finding was that in all but one case, these aberrations have been shown to be also present in the previous specimen despite their lower histopathologi‐

**brain tumors**

154 Neurooncology - Newer Developments

management strategies for meningiomas.

cal grades [88].

Ilhan Yaylim1 , Sumeyya Azam2 , Ammad Ahmad Farooqi3 , Özlem Küçükhüseyin1 , Muhammad Ismail3 and Ali Metin Kafadar4\*

\*Address all correspondence to: ctfkafadar@gmail.com

1 Institute of Experimental Medicine, Department of Molecular Medicine, Istanbul University, Istanbul, Turkey

2 First Affiliated Hospital of Xinjiang Medical University, Xinjiang, Urumqi, PR China

3 Institute of Biomedical and Genetic Engineering (IBGE), Islamabad, Pakistan

<sup>4</sup> Department of Neurosurgery, Cerrahpaşa Medical Faculty, Istanbul University, Istanbul, Turkey
