Abstract 3170: Analysis of copy number variations in meningioma samples using microarrays revealed 22q deletions more frequent in higher grade tumors
Authors: Srovnal Josef , Balik Vladimir , Ehrmann Jiri , Vaverka Miroslav , Hrabalek Lumir , Staffova Katerina , Hajduch Marian 
Published: July 2016

Background: Meningiomas represent one of the most common intracranial tumors. They are generally thought to progress from low to high-grade lesions. However, the molecular mechanisms underlying their pathogenesis remain still uncertain. We suppose the existence of a correlation between the parameters that will help to predict more precisely their biological behavior and response to therapy. Identification of meningioma molecular subgroups may have significant potential to improve clinical management, through molecular disease risk stratification strategies and the identification of patients who could benefit from targeted molecular therapeutics.

Methods and patients: Formalin-fixed paraffin embedded tumor samples were obtained from 30 patients (10 patients in each meningioma grade) and 5 healthy controls (dura mater). Comprehensive clinical-pathological data were mined. There were 7 males and 23 females; mean age was 56.7 years, range 33 - 100 years. Total DNA was purified from FFPE samples after pathological verification using proteinase K treatment followed by QIAmp DNA FFPE Tissue Kit (Qiagen). Microarray analysis was performed using the OncoScan FFPE Assay Kit (Affymetrix), raw data were obtained using Chromosome Analysis Suite (Affymetrix) in default manner. Subsequently, the data were analyzed using Nexus Express software (Biodiscovery). 10 samples were excluded from analyses because of poor quality of results.

Results: In total, 35 OncoScan arrays were performed for copy number variants (CNV) analyses in meningioma and control samples. Our results confirm that del(22q) and del(1p) are the most common (44%, resp. 24% of cases) deletions in meningiomas. Del(22q) was present in 75% grade 2 menigiomas cases in contrast to 25% in grade 1 patients. Additionally, monosomy of chromosome 6 (12%), 8 (8%), 14 (20%) and 18 (12%) were observed. Surprisingly, chromosomal gains and LOH were found only in small portion of cases (8%). Finally, mutation in TP53 (c.817C&gt;T/A, c.637C&gt;T) and PIK3CA (c.3140A&gt;G) genes were found in 12% of cases. Only common CNV variants were found in healthy control samples.

Conclusion: We have identified the CNV profiles in meningioma patients allowing for better knowledge of pathological pathways and tumor progression. Del(22q) is frequently present in higher grade tumors probably altering NF2 a TP53 pathways. However, it will require further validation.

Acknowledgment: This work was financially supported by Ministry of Health of the Czech Republic, grant nr. 15-29021A, IGA UP LF 2015_010 and NPU LO1304.

Citation Format: Josef Srovnal, Vladimir Balik, Jiri Ehrmann, Miroslav Vaverka, Lumir Hrabalek, Katerina Staffova, Marian Hajduch. Analysis of copy number variations in meningioma samples using microarrays revealed 22q deletions more frequent in higher grade tumors. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 3170.