Correlation between Multiparametric MR Imaging and Molecular Genetics in Pontine Pediatric High-Grade Glioma.

BACKGROUND AND PURPOSE: Molecular profiling is a crucial feature in the "integrated diagnosis" of CNS tumors. We aimed to determine whether radiomics could distinguish molecular types of pontine pediatric high-grade gliomas that have similar/overlapping phenotypes on conventional anatomic MR images. MATERIALS AND METHODS: Baseline MR images from children with pontine pediatric high-grade gliomas were analyzed. Retrospective imaging studies included standard precontrast and postcontrast sequences and DTI. Imaging analyses included median, mean, mode, skewness, and kurtosis of the ADC histogram of the tumor volume based on T2 FLAIR and enhancement at baseline. Histone H3 mutations were identified through immunohistochemistry and/or Sanger or next-generation DNA sequencing. The log-rank test identified imaging factors prognostic of survival from the time of diagnosis. Wilcoxon rank-sum and Fisher exact tests compared imaging predictors among groups. RESULTS: Eighty-three patients had pretreatment MR imaging and evaluable tissue sampling. The median age was 6 years (range, 0.7-17 years); 50 tumors had a K27M mutation in H3-3A, and 11, in H3C2/3. Seven tumors had histone H3 K27 alteration, but the specific gene was unknown. Fifteen were H3 wild-type. Overall survival was significantly higher in H3C2/3- compared with H3-3A-mutant tumors (P = .003) and in wild-type tumors compared with any histone mutation (P = .001). Lower overall survival was observed in patients with enhancing tumors (P = .02) compared with those without enhancement. H3C2/3-mutant tumors showed higher mean, median, and mode ADC_total values (P < .001) and ADC_enhancement (P < .004), with lower ADC_total skewness and kurtosis (P < .003) relative to H3-3A-mutant tumors. CONCLUSIONS: ADC histogram parameters are correlated with histone H3 mutation status in pontine pediatric high-grade glioma.

ADC Histogram Analysis of Pediatric Low-Grade Glioma Treated with Selumetinib: A Report from the Pediatric Brain Tumor Consortium.

BACKGROUND AND PURPOSE: Selumetinib is a promising MAP (mitogen-activated protein) kinase (MEK) 1/2 inhibitor treatment for pediatric low-grade gliomas. We hypothesized that MR imaging-derived ADC histogram metrics would be associated with survival and response to treatment with selumetinib. MATERIALS AND METHODS: Children with recurrent, refractory, or progressive pediatric low-grade gliomas who had World Health Organization grade I pilocytic astrocytoma with KIAA1549-BRAF fusion or the BRAF V600E mutation (stratum 1), neurofibromatosis type 1-associated pediatric low-grade gliomas (stratum 3), or sporadic non-neurofibromatosis type 1 optic pathway and hypothalamic glioma (OPHG) (stratum 4) were treated with selumetinib for up to 2 years. Quantitative ADC histogram metrics were analyzed for total and enhancing tumor volumes at baseline and during treatment. RESULTS: Each stratum comprised 25 patients. Stratum 1 responders showed lower values of SD of baseline ADC_total as well as a larger decrease with time on treatment in ADC_total mean, mode, and median compared with nonresponders. Stratum 3 responders showed a greater longitudinal decrease in ADC_total. In stratum 4, higher baseline ADC_total skewness and kurtosis were associated with shorter progression-free survival. When all 3 strata were combined, responders showed a greater decrease with time in ADC_total mode and median. Compared with sporadic OPHG, neurofibromatosis type 1-associated OPHG had lower values of ADC_total mean, mode, and median as well as ADC_enhancement mean and median and higher values of ADC_total skewness and kurtosis at baseline. The longitudinal decrease in ADC_total median during treatment was significantly greater in sporadic OPHG compared with neurofibromatosis type 1-associated OPHG. CONCLUSIONS: ADC histogram metrics are associated with progression-free survival and response to treatment with selumetinib in pediatric low-grade gliomas.

Polymorphisms of p53 promoter and susceptibility to uterine leiomyoma.

BACKGROUND: Uterine leiomyomas could be considered as benign tumor of human uterus smooth muscle with unknown etiology and pathophysiology.Furthermore, they are the most common indication of hysterectomy. The tumor suppressor gene p53 has been involved in various malignancies. Mutation in its promoter site may play a role in tumorigenesis of many malignancies including leiomyompa. MATERIALS AND METHODS: For study of polymorphisms and allele frequency, 234 female patients with pathologically diagnosed uterine leiomyoma and 100 healthy blood donors as control group were assessed. DNAs were extracted from peripheral blood cells, amplified using polymerase chain reaction and restriction fragment length polymorphism (RFLP) technique was utilized for their analysis. RESULT: Proportions of A homozygote/heterozygote/G homozygote for SNP -250 A/G in leiomyoma group were 97.8%, 1.7%, and 0.4%, and in control group 97%, 3%, and 0%, respectively. In case of -216 T/C polymorphism, proportions of T homozygote/heterozygote/C homozygote in leiomyoma were 98%, 1.7%, and 0%, and in control samples 98%, 2%, and 0%, respectively. Genotype frequency of A homozygote/heterozygote/G homozygote for SNP-103 A/G was 97.9%, 1.7%, and 0.4% in leiomyoma group, and 98%, 2%, and 0% in control group, respectively. Proportions of A homozygote/heterozygote/G homozygote for SNP-33 A/G in leiomyoma group were 97.8%, 2.2%, and 0%, and 97%, 3%, and 0% in case samples, respectively. DISCUSSION: Based on the present results in an Iranian female population, surprisingly there was no significant differences between leiomyoma cases and control samples regarding allele frequencies of p53 promoter polymorphism.Therefore, The p53 promoter polymorphism is not associated with the susceptibility of uterine leiomyomas in Iranian women.

Neuroblastoma cells displacement by magnetic carbon nanotubes.

In this paper, as-produced multiwall carbon nanotubes (MWNTs) have been analyzed by scanning electron microscopy and energy dispersive X-ray spectrometry, revealing the presence of Fe, Al, and Zn residuals and impurities. MWNTs have then been dispersed in Pluronic F127 aqueous solution and used to seed neuroblastoma cell lines (HN9.10e and SH-SY5Y) for three days. We found that MWNTs interact with cells and induce, under a permanent constant magnetic field, the cell displacement toward the magnetic source.