These are 1?5, 0.95; 16?4, 1.1 and 85?480, 0.83, respectively. B) Array-CGH profile of a complex set
These are 1?5, 0.95; 16?4, 1.1 and 85?480, 0.83, respectively. B) Array-CGH profile of a complex set of aberrations on chromosome 22, which suggest genetic/cellular heterogeneity within the tumor M90. The regional shifts in fluorescent ratio across chromosome 22 are as summarized with the clone IDs and their ANILFR value; 1?3, 0.95; 24?6, 0.90; 67?14, 0.76; 215?84, 0.88; 285?03, 1.09; 304?26, 0.87; 327?80, 0.76. The non-chromosome 22 autosomal controls have an ANILFR value of 1.00, since this value was used to normalize all values across the genomic array.kb per data point). There may be several possible explanations for these results. One possibility is that additional genes on 22q (other than NF2 tumor suppressor) are important for meningioma development and these are mutated by alternative mechanisms, such as point mutation or epigenetic silencing. Another explanation might be that this subset of samples involves an alternative tumorigenic pthway which does not involve chromosome 22located genes. The current version of the chromosome 22 array has been supplemented with additional non- 22q-derived genomic clones from other chromosomes, which encompass genes(e.g. PTCH2A, PTCH1B, SUFU and DAL1 genes) of potential interest in the fields of meningiomas and brain tumors in general. The complete list of these additional clones is provided in additional file 1. Table 1 shows the samples in which loss of DNA copy number was detected for some of these loci. The highest rate of loss detected was at the PTCH2A locus on 1p34.1, which displayed a rate of loss of 18 . The other loci, namely DAL-1, PTCH1B, SUFU1A and SUFU1B, displayed a level of DNA copy number loss of 6 , 5 , 6 and 6 , respectively. We also detected DNA copy number losses in a number of nonchromosome 22-derived Chaetocin cost control clones. The most frequently deleted control clones were those derived fromPage 9 of(page number not for citation purposes)BMC Genomics 2007, 8:http://www.biomedcentral.com/1471-2164/8/chromosomes 1 and 3, suggesting the likely importance of other regions of the genome in meningioma development/progression.Mutation analysis of NF2 exons and evolutionarily conserved non-genic sequences (CNGs) Inactivating micro-mutations in the NF2 tumor suppressor gene are found in meningiomas of all histopathological subtypes and malignancy grades and are thought to be an early event in tumorigenesis [43]. However, large differences (20?0 ) of mutation frequency in sporadic meningiomas were previously reported [7,13-18]. Our rationale was to reassess the mutation frequency of NF2, especially when combined with very high resolution array-CGH analysis of these tumors. The rationale was also to test the hypothesis that mutations might be located in evolutionarily well conserved non-genic sequences within introns or in the 5′ promoter region of the NF2 gene, in addition to mutations in the exons. Comparisons of the orthologous genomic sequence from the NF2 locus derived from five species (human, baboon, mouse, rat and pufferfish) were previously performed in order to PubMed ID:https://www.ncbi.nlm.nih.gov/pubmed/28404814 identify CNGs that might be of functional impor-tance for the NF2 gene [35]. The exonic sequence of the NF2 gene constitutes 2.7 of this locus. When applying a threshold of 70 sequence identity over >100 bp of gapfree alignment in comparisons between human and mouse, the resulting level of extra-exonic conservation was 3.8 . We selected CNGs for mutational analysis that displayed a similar level of evolutionarily conserv.