Associations of pathological diagnosis and genetic abnormalities in meningiomas with the embryological origins of the meninges

Certain driver mutations and pathological diagnoses are associated with the anatomical site of meningioma, based on which the meninges have different embryological origins. We hypothesized that mutations and pathological diagnoses of meningiomas are associated with different embryological origins. We comprehensively evaluated associations among tumor location, pathological diagnosis (histological type), and genetic alterations including AKT1, KLF4, SMO, POLR2A, and NF2 mutations and 22q deletion in 269 meningioma cases. Based on the embryological origin of meninges, the tumor locations were as follows: neural crest, paraxial mesodermal, and dorsal mesodermal origins. Tumors originating from the dura of certain embryologic origin displayed a significantly different pathological diagnoses and genetic abnormality ratio. For instance, driver genetic mutations with AKT1, KLF4, SMO, and POLR2A, were significantly associated with the paraxial mesodermal origin (p = 1.7 × 10−10). However, meningiomas with NF2-associated mutations were significantly associated with neural crest origin (p = 3.9 × 10–12). On analysis of recurrence, no difference was observed in embryological origin. However, POLR2A mutation was a risk factor for the tumor recurrence (p = 1.7 × 10−2, Hazard Ratio 4.08, 95% Confidence Interval 1.28–13.0). Assessment of the embryological origin of the meninges may provide novel insights into the pathomechanism of meningiomas.

Speech, Surgical, and Psychosocial Considerations for 22Q Deletion Syndrome

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134 Clinicopathological and Molecular Characteristics of Pediatric Versus Adult Meningiomas

INTRODUCTION Molecular and clinical characteristics of pediatric meningiomas are poorly defined. Aim of this study was to analyze clinical features, morphological spectrum and molecular profile of adult and pediatric meningiomas METHODS Sixty four adult and forty pediatric meningiomas from January 2002 to June 2015 were assessed for 1p36 14q32 and 22q deletion by FISH and progesterone receptor (PR), p53 along with MIB-1 LI using immunohistochemistry (IHC). Pediaric cases were also assessed for AKT and SMO mutations by sequencing, and expression of GAB1, stathmin, progesterone receptor (PR) by IHC. RESULTS >In the paediatric group, there were 36 sporadic and 4 NF2 associated meningiomas. Amongst sporadic meningiomas, majority (72.2%) of cases harboured 22q deletion. Difference in frequency of combined 1p/14q deletion in Grade I versus Grade II/III tumors was not significant (13.7% vs 28.5%, P = 0.57). PR immunoreactivity was seen in 65.5% of Grade I and 14.2% of Grade II/III tumors (P = 0.03). Majority (97.2%) of meningiomas were immunonegative for p53. GAB and stathmin co-expression was observed in 58.3% of cases. AKT and SMO mutations were seen in none. Frequency of 1p/14q codeletion was higher in skull base tumours as compared to non skull base meningiomas (23% vs 11.1%, p 0.37). All NF2 meningiomas harboured 22q deletion and showed GAB and stathmin co- expression while none showed 1p/14q loss. In adults, deletion of both 1p and 14q were seen in grade II and grade III convexity meningiomas, in 28.5% and 30% of cases, respectively, while it was absent in grade I convexity tumors. Hormone profile of adult cases was similar to pediatric group. CONCLUSION Pediatric meningiomas share phenotypic and genotypic characteristics with adult counterparts, but GAB and stathmin co-expression in majority of cases and no significant difference in frequency of 1p/14q co-deletion between low and high grade meningiomas indicate inherently aggressive nature. SMO and AKT mutations are distinctly absent.

Atypical 581-kb 22q11.21 Deletion in a Patient with Oculo-Auriculo-Vertebral Spectrum Phenotype

The oculo-auriculo-vertebral spectrum (OAVS) is defined as a group of malformations involving the ears, mouth, mandible, eyes, and cervical spine. Establishing an accurate clinical diagnosis of OAVS is a challenge for clinical geneticists, not only because these patients display heterogeneous phenotypes, but also because its etiology encompasses environmental factors, unknown genetic factors and different chromosome aberrations. To date, several chromosomal abnormalities have been associated with the syndrome, most frequently involving chromosome 22. In the literature, six 22q11.2 microdeletions have been described within the same region, suggesting possible OAVS candidate genes in this segment. Here, we report on a patient with an ∼581-kb 22q11.21 deletion, detected by genomic array and MLPA. This is the 7th case described with OAVS and 22q deletion, suggesting that the 22q11.2 region may be related to the regulation of body symmetry and facial development.