Abstract 2717: Identification of three distinct molecular subtypes in meningioma samples using microarrays for copy-number variants
Authors: Josef Srovnal, Vladimir Balik, Magdalena Houdova Megova, Jiri Ehrmann, Miroslav Vaverka, Lumir Hrabalek, Radek Trojanec, Katerina Staffova, Jana Vrbkova, Marian Hajduch
Journal: Cancer Research (2017)

Abstract Background: Meningioma represents 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. 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 45 meningioma patients and 5 healthy controls (dura mater). Comprehensive clinical-pathological data were mined. There were 15 males and 30 females; median age was 54 years, range 28 - 99 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. The data were analyzed using “R” software, version 3.2.3. Results: Our results confirm that chromosome 22 deletion and del(1p) are the most common (55%, resp. 47% of cases) deletions in meningioma. We revealed chromosomal gains not as rare as was published previously while the dup(3q) was present in 31% of cases. Three meningioma molecular patterns were identified based on CNV profiling - normal-like profile, deletion profile and complex profile. Deletion profile was characterized by loss of 1p and monosomy of chromosomes 6, 10, 14, 18 and 22. The complex profiles combined gains (3q, 8q, chromosomes 12, 15 and 20) and losses (1p, chromosomes 13, 21 and 22). The primary tumor samples of patients with meningioma recurrence (20 patients) had different CNV profile in comparison with patients without recurrence (25 patients). Recurrent tumors had statistically significant higher frequencies of losses on chromosomes 1, 9, 10, 11, 13 and 21 and gains on chromosomes 12, 19 and 20. Moreover, we analyzed CNV profiles of paired tumor samples of 15 recurrent meningioma patients (primary tumor and recurrent tumor in each patient). After extraction, it was found, that the most common alteration in recurrent tumors is chromosome 7q31 and 1p36 gains and chromosome 15q21 losses. Conclusion: We have identified three distinct meningioma molecular patterns - normal-like profile, deletion profile and complex profile. Chromosome 22 deletion, del(1p) and dup(3q) are the most common CNV (55%, 47%, resp. 31% of cases) in meningioma. Potential CNV changes in recurrent meningioma were identified. However, it will require further validation using FISH. Acknowledgment: This work was financially supported by Ministry of Health of the Czech Republic, grant nr. 15-29021A, IGA UP LF 2016_010 and NPU LO1304. Citation Format: Josef Srovnal, Vladimir Balik, Magdalena Houdova Megova, Jiri Ehrmann, Miroslav Vaverka, Lumir Hrabalek, Radek Trojanec, Katerina Staffova, Jana Vrbkova, Marian Hajduch. Identification of three distinct molecular subtypes in meningioma samples using microarrays for copy-number variants [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 2717. doi:10.1158/1538-7445.AM2017-2717