Location of gliomas in relation to mobile telephone use: a case-case and case-specular analysis

The energy absorbed from the radio-frequency fields of mobile telephones depends strongly on distance from the source. The authors' objective in this study was to evaluate whether gliomas occur preferentially in the areas of the brain having the highest radio-frequency exposure. The authors used 2 approaches: In a case-case analysis, tumor locations were compared with varying exposure levels; in a case-specular analysis, a hypothetical reference location was assigned for each glioma, and the distances from the actual and specular locations to the handset were compared. The study included 888 gliomas from 7 European countries (2000-2004), with tumor midpoints defined on a 3-dimensional grid based on radiologic images. The case-case analyses were carried out using unconditional logistic regression, whereas in the case-specular analysis, conditional logistic regression was used. In the case-case analyses, tumors were located closest to the source of exposure among never-regular and contralateral users, but not statistically significantly. In the case-specular analysis, the mean distances between exposure source and location were similar for cases and speculars. These results do not suggest that gliomas in mobile phone users are preferentially located in the parts of the brain with the highest radio-frequency fields from mobile phones.     

Founder population-specific HapMap panel increases power in GWA studies through improved imputation accuracy and CNV tagging

The combining of genome-wide association (GWA) data across populations represents a major challenge for massive global meta-analyses. Genotype imputation using densely genotyped reference samples facilitates the combination of data across different genotyping platforms. HapMap data is typically used as a reference for single nucleotide polymorphism (SNP) imputation and tagging copy number polymorphisms (CNPs). However, the advantage of having population-specific reference panels for founder populations has not been evaluated. We looked at the properties and impact of adding 81 individuals from a founder population to HapMap3 reference data on imputation quality, CNP tagging, and power to detect association in simulations and in an independent cohort of 2138 individuals. The gain in SNP imputation accuracy was highest among low-frequency markers (minor allele frequency [MAF] < 5%), for which adding the population-specific samples to the reference set increased the median R² between imputed and genotyped SNPs from 0.90 to 0.94. Accuracy also increased in regions with high recombination rates. Similarly, a reference set with population-specific extension facilitated the identification of better tag-SNPs for a subset of CNPs; for 4% of CNPs the R² between SNP genotypes and CNP intensity in the independent population cohort was at least twice as high as without the extension. We conclude that even a relatively small population-specific reference set yields considerable benefits in SNP imputation, CNP tagging accuracy, and the power to detect associations in founder populations and population isolates in particular.In the next generation of genome-wide association studies (GWAS), large consortia combine GWA results from platforms that have different single nucleotide polymorphism (SNP) marker resolutions and the capability for copy number polymorphism (CNP) discovery and genotyping (Cooper et al. 2008). The challenge of having data of different SNP resolutions across GWA studies can be overcome by genotype imputation: the inference of missing and unobserved data from the local linkage disequilibrium (LD) structure of a high-resolution reference sample (Li and Abecasis 2006; Marchini et al. 2007). Similarly, information on CNPs can be inferred from the variation of SNPs that correlate with CNP signal intensities in a reference set genotyped with a high-density array with good CNP coverage (Locke et al. 2006; McCarroll et al. 2006; Redon et al. 2006). The strategy of inferring CNPs from SNP data may assist future CNP studies by allowing for the determination of CNPs using a specific set of tagging SNPs instead of costly CNP detection and genotyping pipelines.In studies using samples of European origin, the SNP imputation and CNP-tagging reference panel has typically been the 60 CEPH (Utah residents with ancestry from Northern and Western Europe, abbreviation: CEU) samples from HapMap Phase 2 (The International HapMap Consortium 2003, 2007). Recently, additional HapMap populations were genotyped with two commercially available chips, the Illumina Infinium Human1M-single and Affymetrix Genome-Wide Human SNP Array 6.0 (The International HapMap 3 Consortium 2010). This new HapMap3 data set of 1184 samples offers better genomic information due to its increased sample size and the SNP and CNP data from the high-density genotyping arrays. The design of HapMap3 allows for the extension of the reference set into additional populations with different LD structures. Some of the most unique LD patterns in the world arise in founder populations (Service et al. 2006), many of which also display unique health risks (Peltonen et al. 1999; Orton et al. 2008). Given these characteristics, does it make sense for a founder population to have its own reference set and, if so, how would this impact our ability to detect disease variants? Here, we use a local reference set from the genetically distinct Finnish founder population (Supplemental Fig. 1; Service et al. 2006; Jakkula et al. 2008) to evaluate the accuracy, coverage, and power of SNP imputation and CNP tagging relative to that of the less-specific HapMap3 European samples CEU and TSI (from Tuscans in Italy).     

Desmoplastic infantile ganglioglioma: novel aspects in clinical presentation and genetics

BACKGROUND: Desmoplastic infantile ganglioglioma is a rare tumor occurring mainly in infants and young children. Both radiological and histopathological appearances may resemble malignancy, although its clinical course is mainly benign. METHODS: Altogether, 5 cases of DIG have been operated on in our hospital since the first diagnosis of DIG in Finland in 1993. We evaluated their presenting symptoms, radiological and surgical findings, histologic characteristics, and follow-up. RESULTS: All patients were male. Three were less than 18 months old, and 2 were 35 and 79 months old. The most common presenting symptoms were epileptic seizures (4 cases). In 4 cases, there was a histopathologically verified single cystic tumor. In 1 case, DIG was operatively diagnosed in 2 separate locations. This patient, moreover, had 2 other lesions suspected of being DIG, including a mass originating from the ophthalmic nerve. None of the patients received adjuvant therapies. All our patients are alive after 7 to 120 months of follow-up. There were no recurrences in any of the patients after tumor resection. For the first time, we describe EGFR and MYCN amplifications in tumors which are, respectively, of their mixed glial and neuronal origin. CONCLUSION: The clinical presentation of DIG may be more often associated with epileptic seizures than previously thought. The radiological appearance of DIG may vary from cystic to solid and from contrast-enhancing to nonenhancing. Even multiple locations of DIG have been encountered. Increasing evidence supports surgery as the treatment of choice for DIG, although oncogene amplifications have been described.