Type I and Ir pleuropulmonary blastoma (PPB): A report from the International PPB/DICER1 Registry.

BACKGROUND: Pleuropulmonary blastoma (PPB) is the most common lung cancer of infancy and early childhood. Type I PPB is a purely cystic lesion that has a microscopic population of primitive small cells with or without rhabdomyoblastic features and may progress to type II or III PPB, whereas type Ir lacks primitive small cells. METHODS: Children with suspected PPB were enrolled in the International PPB/DICER1 Registry. Pathology was centrally reviewed, and follow-up was ascertained annually. RESULTS: Between 2006 and 2022, 205 children had centrally reviewed type I or Ir PPB; 39% of children with type I and 5% of children with type Ir PPB received chemotherapy. Outcomes were favorable, although 11 children (nine with type I and two with type Ir PPB) experienced progression to type II/III (n = 8) or regrowth of type I PPB at the surgical site (n = 3), none of whom received chemotherapy before progression. Age and cyst size in combination were more suitable than either factor alone in predicting whether a particular lesion was type I or Ir PPB. CONCLUSIONS: For young children with type I PPB, outcomes are favorable, but complete resection is indicated because of the risk for progression. Chemotherapy may be useful in a subset of children at increased risk for recurrence/progression. Efforts to risk stratify children with type I PPB to optimize outcomes while reducing treatment-related side effects are underway.

RELATIONSHIP BETWEEN INTEGRITY OF HENLE FIBERS AND VISUAL ACUITY IN MYOPIC FOVEOSCHISIS.

BACKGROUND: To analyze the relationship between Henle fiber (HF) integrity and visual acuity in highly myopic eyes with foveoschisis. METHODS: Three hundred and fifty-eight highly myopic eyes were included in this study and divided into three groups according to the Triton optical coherence tomography results. Group 1 included 19 eyes with myopic foveoschisis where the inner and outer retina were connected by a columnar structure in the HF layer at the foveolar area. Group 2 included 17 eyes with myopic foveoschisis where the columnar structure was disrupted in the HF layer at the foveolar area. Group 3 included 322 eyes without myopic foveoschisis or other ocular disease. Clinical and optical coherence tomography findings were obtained and compared. RESULTS: Eyes with vitreomacular traction, arteriolar traction, and longer axial length were more likely to have myopic foveoschisis with intact columnar structure in the HF layer (odds ratio [OR], 12.84; P = 0.001; OR, 7.63; P = 0.04; OR, 2.03; P = 0.03) and with disrupted columnar structure in the HF layer (OR, 65.21; P = 0.001; OR, 6.60; P = 0.02; OR, 2.63; P = 0.01). Moreover, eyes with disrupted columnar structure in the HF layer presented a lower best-corrected visual acuity (P = 0.001), longer axial length (P = 0.001; P = 0.009), higher central foveolar thickness (P = 0.001; P = 0.02), and a higher prevalence of vitreomacular traction (P = 0.001; P = 0.04) than control or integrity HF eyes. Furthermore, worse best-corrected visual acuity was related to myopic foveoschisis with disrupted columnar structure in the HF layer (P < 0.01). CONCLUSION: The integrity of HF in patients with myopic foveoschisis appears to play an important role in visual acuity.

Correlation between retinal nerve fibre layer thickness and white matter lesions in Alzheimer's disease.

OBJECTIVES: Early diagnosis in Alzheimer's disease (AD) is crucial in order to implement new therapeutic strategies. The retina is embryologically related to the brain. Thus, the possible usefulness of optical coherence tomography (OCT) in the early detection of AD is currently being studied. Our aim was to study the relationship between retinal nerve fiber layer (RNFL) thickness and AD. METHODS: We undertook an observational, analytical, cross-sectional study with consecutive sampling of 32 patients with AD or mild cognitive impairment and a group of healthy controls (C). The total number of eyes studied was 64. An ophthalmological and a comprehensive neuropsychological evaluation were performed in all participants. Quantification of white matter lesions and study of atrophy of the hippocampus by cerebral magnetic resonance were also performed. RESULTS: We observed a significant linear trend towards a thinning of RNFL as the degree of cognitive deterioration increased, in the superior and temporal quadrants of the retina. A significant correlation was also noted between the mean thickness of the RNFL of the left temporal quadrant and occipital white matter lesions (r = -0.579, p = 0.038). CONCLUSIONS: OCT could be a safe, rapid noninvasive tool providing useful biomarkers in the early detection of cognitive deterioration and AD.

Laparoscopic sleeve gastrectomy in morbidly obese adolescents: Initial experience of a Pediatric Multidisciplinary Unit.

INTRODUCTION: Childhood obesity is a significant health problem worldwide, associated with significant metabolic and cardiovascular morbidity. Recent evidence points to metabolic and bariatric surgery as a safe and effective treatment for morbidly obese adolescents. We aim to report the initial results after laparoscopic sleeve gastrectomy (LSG) for adolescent patients in a pediatric center. MATERIAL AND METHODS: Retrospective data review of patients younger than 19 years who underwent LSG for treatment of morbid obesity between 2013 and 2019. RESULTS: A total of 16 adolescents (12 female, 4 male) with a median age of 17.5 years underwent LSG. Median preoperative weight and body mass index were 129kg and 48.6kg/m-2, respectively. All patients had at least one comorbidity. Median follow-up was 18.5 months. The overall percent total weight loss was 32.5% and percent excess weight loss was 68%. Resolution of comorbidities was noted in the majority of patients. No perioperative complications were reported. CONCLUSIONS: Laparoscopic sleeve gastrectomy is a safe and effective option for treatment of morbidly obese adolescents, resulting in significant weight loss and comorbidity resolution with a low risk of complications.

Multicenter validation study of the WINROP algorithm as a method for detecting retinopathy of prematurity.

Purpose: To assess the validity of the online WINROP algorithm in two Spanish populations of premature infants.Materials and methods: The study population consisted of 502 premature infants born in the San Cecilio University Hospital of Granada and the Regional University Hospital of Málaga in the years 2000-2015. The WINROP algorithm was used to determine an alarm threshold for retinopathy of prematurity (ROP). The results were compared with those obtained from serial examinations of premature infants.Results: The global WINROP algorithm showed a sensitivity of 62%, specificity of 74%, positive predictive value (PPV) of 59%, and negative predictive value (NPV) of 77%. This algorithm showed a greater sensitivity (76%) to identify severe ROP.Conclusions: The WINROP screening algorithm in this study showed moderate sensitivity, so many ROP cases amenable to treatment were not detected. Other criteria should be added to the algorithm to increase the sensitivity.

FACTORS ASSOCIATED WITH SEROUS RETINAL DETACHMENT IN HIGHLY MYOPIC EYES WITH VERTICAL OVAL-SHAPED DOME.

PURPOSE: This study investigated factors associated with persistent serous retinal detachment in highly myopic eyes with vertical oval-shaped domes. METHODS: Twenty-eight highly myopic patients (40 eyes) with smooth macular elevations related to a vertical oval-shaped dome were recruited. Serous retinal detachment was investigated; 11 eyes had persistent submacular fluid (study group) and 29 eyes lacked submacular fluid (control group). All patients underwent complete ophthalmologic examinations, including axial-length measurement and fluorescein angiography. Spectral domain optical coherence tomography scans through the fovea measured choroidal thicknesses, macular bulge height, and vitreoretinal interface factors. RESULTS: No studied variables (age, sex, spherical equivalence, axial length, vitreomacular traction, epiretinal membrane, and internal limiting membrane detachment) except higher macular bulge height (P = 0.03) and a reduced macular choroidal thickness (P = 0.02) were associated with the risk of serous retinal detachment. No statistically significant differences in best-corrected visual acuity were observed between the study and control groups. Serous retinal detachment always occurred at the top of the inward incurvation of the macula and was characterized by multiple hyperfluorescent granular patches on fluorescein angiography. CONCLUSION: A higher macular bulge height and a reduced macular choroidal thickness might be important factors in the development of serous retinal detachment in patients with vertical oval-shaped domes.

Characterization of endolymphatic sac tumors and von Hippel-Lindau disease in the International Endolymphatic Sac Tumor Registry.

BACKGROUND: Endolymphatic sac tumors (ELSTs) are, with a prevalence of up to 16%, a component of von Hippel-Lindau (VHL) disease. Data from international registries regarding heritable fraction and characteristics, germline VHL mutation frequency, and prevalence are lacking. METHODS: Systematic registration of ELSTs from international centers of otorhinolaryngology and from multidisciplinary VHL centers' registries was performed. Molecular genetic analyses of the VHL gene were offered to all patients. RESULTS: Our population-based registry comprised 93 patients with ELST and 1789 patients with VHL. The prevalence of VHL germline mutations in apparently sporadic ELSTs was 39%. The prevalence of ELSTs in patients with VHL was 3.6%. ELST was the initial manifestation in 32% of patients with VHL-ELST. CONCLUSION: Prevalence of ELST in VHL disease is much lower compared to the literature. VHL-associated ELSTs can be the first presentation of the syndrome and mimic sporadic tumors, thus emphasizing the need of molecular testing in all presentations of ELST. © 2015 Wiley Periodicals, Inc. Head Neck 38: 673-679, 2016.

Genome-wide methylation analysis in vestibular schwannomas shows putative mechanisms of gene expression modulation and global hypomethylation at the HOX gene cluster.

Schwannomas are tumors that develop from Schwann cells in the peripheral nerves and commonly arise from the vestibular nerve. Vestibular schwannomas can present unilaterally and sporadically or bilaterally when the tumor is associated with neurofibromatosis Type 2 (NF2) syndrome. The molecular hallmark of the disease is biallelic inactivation of the NF2 gene. The epigenetic signature of schwannomas remains poorly understood and is mostly limited to DNA methylation of the NF2 gene, whose altered expression due to epigenetic factors in this tumor is controversial. In this study, we tested the genomewide DNA methylation pattern of schwannomas to shed light on this epigenetic alteration in these particular tumors. The methodology used includes Infinium Human Methylation 450K BeadChip microarrays in a series of 36 vestibular schwannomas, 4 nonvestibular schwannomas, and 5 healthy nerves. Our results show a trend toward hypomethylation in schwannomas. Furthermore, homeobox (HOX) genes, located at four clusters in the genome, displayed hypomethylation in several CpG sites in the vestibular schwannomas but not in the nonvestibular schwannomas. Several microRNA (miRNA) and protein-coding genes were also found to be hypomethylated at promoter regions and were confirmed as upregulated by expression analysis; including miRNA-21, Met Proto-Oncogene (MET), and PMEPA1. We also detected methylation patterns that might be involved in alternative transcripts of several genes such as NRXN1 or MBP, which would increase the complexity of the methylation and expression patterns. Overall, our results show specific epigenetic signatures in several coding genes and miRNAs that could potentially be used as therapeutic targets.

Global expression profile in low grade meningiomas and schwannomas shows upregulation of PDGFD, CDH1 and SLIT2 compared to their healthy tissue.

Schwannomas and grade I meningiomas are non­metastatic neoplasms that share the common mutation of gene NF2. They usually appear in neurofibromatosis type 2 patients. Currently, there is no drug treatment available for both tumors, thus the use of wide expression technologies is crucial to identify therapeutic targets. Affymetrix Human Gene 1.0 ST was used to test global gene expression in 22 meningiomas, 31 schwannomas and, as non-tumoral controls, 3 healthy meningeal tissues, 8 non-tumoral nerves and 1 primary Schwann cell culture. A non-stringent P-value cut-off and fold change were used to establish deregulated genes. We identified a subset of genes that were upregulated in meningiomas and schwannomas when compared to their respectively healthy tissues, including PDGFD, CDH1 and SLIT2. Thus, these genes should be thoroughly studied as targets in a possible combined treatment.

Gene expression analysis of aberrant signaling pathways in meningiomas.

Examining aberrant pathway alterations is one method for understanding the abnormal signals that are involved in tumorigenesis and tumor progression. In the present study, expression arrays were performed on tumor-related genes in meningiomas. The GE Array Q Series HS-006 was used to determine the expression levels of 96 genes that corresponded to six primary biological regulatory pathways in a series of 42 meningiomas, including 32 grade I, four recurrent grade I and six grade II tumors, in addition to three normal tissue controls. Results showed that 25 genes that were primarily associated with apoptosis and angiogenesis functions were downregulated and 13 genes frequently involving DNA damage repair functions were upregulated. In addition to the inactivation of the neurofibromin gene, NF2, which is considered to be an early step in tumorigenesis, variations of other biological regulatory pathways may play a significant role in the development of meningioma.

Global profiling in vestibular schwannomas shows critical deregulation of microRNAs and upregulation in those included in chromosomal region 14q32.

BACKGROUND: Vestibular schwannomas are benign tumors that arise from Schwann cells in the VIII cranial pair and usually present NF2 gene mutations and/or loss of heterozygosity on chromosome 22q. Deregulation has also been found in several genes, such as ERBB2 and NRG1. MicroRNAs are non-coding RNAs approximately 21 to 23 nucleotides in length that regulate mRNAs, usually by degradation at the post-transcriptional level. METHODS: We used microarray technology to test the deregulation of miRNAs and other non-coding RNAs present in GeneChip miRNA 1.0 (Affymetrix) over 16 vestibular schwannomas and 3 control-nerves, validating 10 of them by qRT-PCR. FINDINGS: Our results showed the deregulation of 174 miRNAs, including miR-10b, miR-206, miR-183 and miR-204, and the upregulation of miR-431, miR-221, miR-21 and miR-720, among others. The results also showed an aberrant expression of other non-coding RNAs. We also found a general upregulation of the miRNA cluster located at chromosome 14q32. CONCLUSION: Our results suggest that several miRNAs are involved in tumor formation and/or maintenance and that global upregulation of the 14q32 chromosomal site contains miRNAs that may represent a therapeutic target for this neoplasm.

Microarray analysis of gene expression in vestibular schwannomas reveals SPP1/MET signaling pathway and androgen receptor deregulation.

Vestibular schwannomas are benign neoplasms that arise from the vestibular nerve. The hallmark of these tumors is the biallelic inactivation of neurofibromin 2 (NF2). Transcriptomic alterations, such as the neuregulin 1 (Nrg1)/ErbB2 pathway, have been described in schwannomas. In this study, we performed a whole transcriptome analysis in 31 vestibular schwannomas and 9 control nerves in the Affymetrix Gene 1.0 ST platform, validated by quantitative real-time PCR (qRT-PCR) using TaqMan low density arrays. We performed a mutational analysis of NF2 by PCR/denaturing high-performance liquid chromatography (dHPLC) and multiplex ligation-dependent probe amplification (MLPA), as well as a microsatellite marker analysis of the loss of heterozygosity (LOH) of chromosome 22q. The microarray analysis demonstrated that 1,516 genes were deregulated and 48 of the genes were validated by qRT-PCR. At least 2 genetic hits (allelic loss and/or gene mutation) in NF2 were found in 16 tumors, seven cases showed 1 hit and 8 tumors showed no NF2 alteration. MET and associated genes, such as integrin, alpha 4 (ITGA4)/B6, PLEXNB3/SEMA5 and caveolin-1 (CAV1) showed a clear deregulation in vestibular schwannomas. In addition, androgen receptor (AR) downregulation may denote a hormonal effect or cause in this tumor. Furthermore, the osteopontin gene (SPP1), which is involved in merlin protein degradation, was upregulated, which suggests that this mechanism may also exert a pivotal role in schwannoma merlin depletion. Finally, no major differences were observed among tumors of different size, histological type or NF2 status, which suggests that, at the mRNA level, all schwannomas, regardless of their molecular and clinical characteristics, may share common features that can be used in their treatment.

Expression analysis of tumor-related genes involved in critical regulatory pathways in schwannomas.

PURPOSE: Gene expression array analysis is providing key data on the potential candidate genes and biological pathways involved in schwannoma origin and development. In this way we performed expression array studies on tumor-related genes in schwannomas. METHODS: The GE Array Q Series HS-006 (SuperArray, Bethesda, MD, USA) was used to determine the expression levels of 96 genes corresponding to 6 primary biological regulatory pathways in a series of 23 schwannomas. RESULTS: We identified 15 genes down-regulated, primarily corresponding to signal transduction functions, and 26 genes up-regulated, most frequently involving cell adhesion functions. CONCLUSIONS: In addition to the NF2 inactivation (considered as an early step), variations of other biological regulatory pathways might play a key role in schwannoma.

Research resource: Transcriptional profiling reveals different pseudohypoxic signatures in SDHB and VHL-related pheochromocytomas.

The six major genes involved in hereditary susceptibility for pheochromocytoma (PCC)/paraganglioma (PGL) (RET, VHL, NF1, SDHB, SDHC, and SDHD) have been recently integrated into the same neuronal apoptotic pathway where mutations in any of these genes lead to cell death. In this model, prolyl hydroxylase 3 (EglN3) abrogation plays a pivotal role, but the molecular mechanisms underlying its inactivation are currently unknown. The aim of the study was to decipher specific alterations associated with the different genetic classes of PCCs/PGLs. With this purpose, 84 genetically characterized tumors were analyzed by means of transcriptional profiling. The analysis revealed a hypoxia-inducible factor (HIF)-related signature common to succinate dehydrogenase (SDH) and von Hippel-Lindau (VHL) tumors, that differentiated them from RET and neurofibromatosis type 1 cases. Both canonical HIF-1α and HIF-2α target genes were overexpressed in the SDH/VHL cluster, suggesting that a global HIF deregulation accounts for this common profile. Nevertheless, when we compared VHL tumors with SDHB cases, which often exhibit a malignant behavior, we found that HIF-1α target genes showed a predominant activation in the VHL PCCs. Expression data from 67 HIF target genes was sufficient to cluster SDHB and VHL tumors into two different groups, demonstrating different pseudo-hypoxic signatures. In addition, VHL-mutated tumors showed an unexpected overexpression of EglN3 mRNA that did not lead to significantly different EglN3 protein levels. These findings pave the way for more specific therapeutic approaches for malignant PCCs/PGLs management based on the patient's genetic alteration.

Genomic deletions at 1p and 14q are associated with an abnormal cDNA microarray gene expression pattern in meningiomas but not in schwannomas.

The molecular pathology of meningiomas and shwannomas involve the inactivation of the NF2 gene to generate grade I tumors. Genomic losses at 1p and 14q are observed in both neoplasms, although more frequently in meningiomas. The inactivation of unidentified genes located in these regions appears associated with tumor progression in meningiomas, but no clues to its molecular/clinical meaning are available in schwannomas. Recent microarray gene expression studies have demonstrated the existence of molecular subgroups in both entities. In the present study, we correlated the presence of genomic deletions at 1p, 14q, and 22q with the expression patterns of 96 tumor-related genes obtained by cDNA low-density microarrays in a series of 65 tumors including 42 meningiomas and 23 schwannomas. Two expression pattern groups were identified by cDNA mycroarray analysis when compared to the expression pattern in normal control RNA in both meningiomas and schwannomas, each one with patterns similar and different from the normal control. Meningioma and schwannoma subgroups differed in the expression of 38 and 16 genes, respectively. Using MLPA and microsatellites, we identified genomic losses at 1p, 14q, and 22q at nonrandom frequencies (12.5-69%) in meningiomas and schwannomas. Losses at 22q were almost equally frequent in both molecular expression subgroups in both neoplasms. However, deletions at 1p and 14q accumulated in meningiomas with a gene expression pattern different from the normal pattern, whereas the inverse situation occurred in schwannomas. Those anomalies characterized the schwannomas with expression pattern similar to the normal control. These findings suggest that deletions at 1p and 14q enhance the development of an abnormal tumor-related gene expression pattern in meningiomas, but this fact is not corroborated in schwannomas.

Head and neck paragangliomas in von Hippel-Lindau disease and multiple endocrine neoplasia type 2.

BACKGROUND: Head and neck paragangliomas (HNPs) occur as sporadic or familial entities, the latter mostly in association with germline mutations of the SDHB, SDHC, or SDHD (SDHx) genes. Heritable non-SDHx HNP might occur in von Hippel-Lindau disease (VHL, VHL gene), multiple endocrine neoplasia type 2 (MEN2, RET gene), and neurofibromatosis type 1 (NF1, NF1 gene). Reports of non-SDHx HNP presentations are scarce and guidance for genetic testing nonexistent. PATIENTS AND METHODS: An international consortium registered patients with HNPs and performed mutation analyses of the SDHx, VHL, and RET genes. Those with SDHx germline mutations were excluded for purposes of this study. Personal and family histories were evaluated for paraganglial tumors, for the major tumor manifestations, and for family history of VHL, MEN2, or NF1. RESULTS: Twelve patients were found to have hereditary non-SDHx HNPs of a total of 809 HNP and 2084 VHL registrants, 11 in the setting of germline VHL mutations and one of a RET mutation. The prevalence of hereditary HNP is five in 1000 VHL patients and nine in 1000 non-SDHx HNP patients. Comprehensive literature review revealed previous reports of HNPs in five VHL, two MEN2, and one NF1 patient. Overall, 11 here presented HNP cases, and four previously reported VHL-HNPs had lesions characteristic for VHL and/or a positive family history for VHL. CONCLUSIONS: Our observations provide evidence that molecular genetic testing for VHL or RET germline mutations in patients with HNP should be done only if personal and/or family history shows evidence for one of these syndromes.

Allelic status of 1p and 19q in oligodendrogliomas and glioblastomas: multiplex ligation-dependent probe amplification versus loss of heterozygosity.

Identification of the 1p/19q allelic status in gliomas, primarily those with a major oligodendroglial component, has become an excellent molecular complement to tumor histology in order to identify those cases sensitive to chemotherapy. In addition to loss of heterozygosity (LOH), fluorescence in situ hybridization (FISH), or comparative genomic hybridization (CGH), multiplex ligation-dependent probe amplification (MLPA) has been shown to be an alternative methodology to identify deletions of those chromosome arms. We used MLPA to explore the 1p and 19q allelic constitution in a series of 76 gliomas: 41 tumors with a major oligodendroglial component, 34 glioblastomas, and one low-grade astrocytoma. We compared the MLPA findings of the oligodendroglial cases with those previously obtained using LOH in the same samples. Thirty-eight of 41 oligodendrogliomas displayed identical findings by both LOH and MLPA, and losses at either 1p and/or 19q were identified in 12 of 35 (34%) astrocytic tumors. These findings agree with data previously reported comparing MLPA versus FISH or CGH in gliomas and suggest that MLPA can be used in the identification of the 1p/19q allelic deletions on these brain neoplasms.

[No-malignant lessions involving the paranasal sinuses and anterior skull base]. / Lesiones no malignas que implican a senos paranasales y fosa craneal anterior.

BACKGROUND AND OBJECTIVES: The lesions that involve the paranasal sinuses and the anterior cranial base at the same time are not unusual. These diseases have different features. The aim of this study is to set out the particularities of the non-malignant lesions involving both zones. MATERIAL AND METHODS: Retrospective study of 32 patients between 1986 and 2007 diagnosed with: non-malignant tumours (31.2 %), tumorlike lesions (3.1 %), fibrous-osseous lesions (12.5 %), congenital or acquired malformations (18.7 %) and infection disease (34.3 %). We analyse the diagnostic imaging, the treatment and pathogen mechanism. RESULTS: Only 6 of 43 osteomas involved the paranasal sinuses and anterior cranial fossa (13.04 %): 3 cases have developed meningitis and 1 developed a pneumocephalus. 2 cases are meningiomas: 1 was asymptomatic and the other one caused destruction at subtotal frontal bone. 1 giant hemangioma associated with Klippel-Trenaunay syndrome is treated by combined craniofacial approach. The fibrous-osseous lesions were specifically fibrous dysplasia and affected the ethmoides. The encephalocele were predominating in the malformations group, 2 were diagnosed after repeated meningitis. 11 cases are included by infection: 10 cases caused osteomielitis and the eleventh is a patient with a mucormycosis. Surgery has been used in 84.3 % of the cases: frontal craniotomy 37 %, combined craniofacial approach 18.5 %, subfrontal approach 18.5 %, osteoplastic technique 18.5 %, lateronasal approach 3.7 %, endonasal microscopic resection 3.7 %. CONCLUSIONS: In this study the diagnosis, extension and surgical management were supported in the imaging. A closed separation between the anterior cranial fossa ant the sinus is necessary after the resection. The reconstruction was performed using a pedicled pericranial flap and titanium mesh in most of the cases.

Meningiomas and schwannomas: molecular subgroup classification found by expression arrays.

Microarray gene expression profiling is a high-throughput system used to identify differentially expressed genes and regulation patterns, and to discover new tumor markers. As the molecular pathogenesis of meningiomas and schwannomas, characterized by NF2 gene alterations, remains unclear and suitable molecular targets need to be identified, we used low density cDNA microarrays to establish expression patterns of 96 cancer-related genes on 23 schwannomas, 42 meningiomas and 3 normal cerebral meninges. We also performed a mutational analysis of the NF2 gene (PCR, dHPLC, Sequencing and MLPA), a search for 22q LOH and an analysis of gene silencing by promoter hypermethylation (MS-MLPA). Results showed a high frequency of NF2 gene mutations (40%), increased 22q LOH as aggressiveness increased, frequent losses and gains by MLPA in benign meningiomas, and gene expression silencing by hypermethylation. Array analysis showed decreased expression of 7 genes in meningiomas. Unsupervised analyses identified 2 molecular subgroups for both meningiomas and schwannomas showing 38 and 20 differentially expressed genes, respectively, and 19 genes differentially expressed between the two tumor types. These findings provide a molecular subgroup classification for meningiomas and schwannomas with possible implications for clinical practice.