ABSTRACT: High copy number variation burdens in cranial meningiomas from patients with diverse clinical phenotypes characterized by hot genomic structure changes
Project description:High copy number variation burdens in cranial meningiomas from patients with diverse clinical phenotypes characterized by hot genomic structure changes
Project description:Genome-wide genotyping analysis identified copy number variations in cranial meningiomas in Chinese patients, and demonstrated diverse CNV burdens among individuals with diverse clinical features.
Project description:Meningiomas, as the most common primary tumor of the central nervous system, are known to harbor genomic aberrations that associate with clinical phenotypes. Here we performed genome-wide genotyping for cranial meningiomas in 383 Chinese patients and identified 9,821 copy number variations (CNVs).
Project description:Cytogenetic profiles of 50 meningiomas using high-density GeneChip Mapping 500K set and Genome-Wide Human SNP 6.0 Array in the tumor tissues and in the peripheral blood of the same patients. A total of two hundred 500k arrays (100 tumor samples and 100 blood samples) and 14 SNP6.0 arrays (7 tumour samples and 7 peripheral blood samples) were studied to explore the most common recurrent chromosomal abnormalities (gains and losses) in meningiomas. Our results confirm that del(22q) (52%) and del(1p) (16%) (common deleted regions: 22q11.21-22q13.3. and 1p31.2-p36.33) are the most frequent abnormalities. Additionally, recurrent monosomy 14 (8%), del(6p) (10%), del(7p) (10%) and del(19p) (6%) were also observed, while copy number variation (CNV) patterns consistent with recurrent chromosome gains, gene amplification was absent or rare. Based on their overall SNP profiles meningiomas could be classified into: i) diploid cases, ii) meningiomas with a single chromosome change (e.g. monosomy 22/del(22q) and iii) tumours with M-bM-^IM-%2 altered chromosomes. 500K SNP mapping set array and Genome-Wide Human SNP 6.0 Array were used to profile 50 meningiomas with matched blood DNA samples. Loss of heterozygosity (LOH) and copy number abnormality (CNA) profiles were derived from each tumour-blood pair. In seven tumors, both types of arrays were assessed.
Project description:Meningiomas in pediatric and adolescent/young adult patients are poorly characterized biologically and clinically, and risk stratification is largely extrapolated from adult tumors. We analyzed 293 tumors from patients aged 0–39 years using integrated histopathological and molecular profiling. Youth-onset meningiomas were enriched for NF2 and SMARCE1 alterations and exhibited a gain-dominated copy-number landscape, including recurrent chr17q gain, whereas canonical adult high-risk features, such as chr1p loss, lacked prognostic significance. Adult-derived prognostic frameworks—including WHO grade, methylation-based stratification, and integrated risk scores—failed to predict progression in patients ≤21 years. Tumors segregated into age-enriched epigenetic clusters defined by SMARCE1, NF2, and BAP1 alterations. Among NF2-altered tumors, patterns of Merlin inactivation shaped by germline status and co-occurring copy-number variations delineated biologically divergent subsets. Across all groups, extent of resection remained the strongest predictor of outcome. These findings define pediatric and young adult meningiomas as a distinct molecular entity requiring age-adapted risk stratification.