2037

EPB41L2

4.1-G|4.1G;erythrocyte membrane protein band 4.1-like 2;EPB41L2;erythrocyte membrane protein band 4.1-like 2

band 4.1-like protein 2|erythrocyte membrane protein band 4.1 like-protein 2|generally expressed protein 4.1

6q23

protein-coding

Ependymomas are common pediatric and adult CNS malignancies with a wide biologicspectrum that is often hard to predict using classic prognostic variables. The molecular pathogenesis is also poorly understood and few reproducible genetic alterations have been identified. The most common genetic alteration has been the loss of the Protein 4.1 family member, NF2, predominantly in spinal ependymomas.In contrast, a pilot study suggested that 4.1B deletions might be more common inintracranial ependymomas. These findings prompted us to study Protein 4.1 familymembers (NF2, 4.1B, 4.1R, 4.1G) in a larger cohort of 84 ependymomas (51 intracranial and 33 spinal; 11 WHO grade I, 43 grade II, 30 grade III). Fluorescence in situ hybridization was performed using NF2, 4.1B, 4.1R and 4.1G probes and immunohistochemical staining was performed in a subset using merlin, Protein 4.1B and Protein 4.1R antibodies. Additionally, frozen tissue from nine ependymomas (four intracranial and five spinal) was obtained for Western blot analysis for merlin, 4.1B and 4.1R expression. The majority of cases harbored one or more detectable genetic alterations, but we found that 4.1B gene deletions and 4.1R loss of expression were statistically more common in the pediatric vs adult, intracranial vs spinal, and grade III vs grade I/II subsets (P-values of 0.038 to <0.001). Also, 4.1G deletions were seen in 11/27 (41%) patients who either died of disease or had residual/recurrent tumor vs 5/41 patients with no evidence of disease at last follow-up (P=0.009). We conclude that alterations of Protein 4.1family members are common in ependymal tumors and that specific alterations are associated with distinct clinicopathologic subsets.

We conducted a genome-wide association study of childhood acute lymphoblastic leukemia (ALL) in a case-control study conducted in Korea. Incident childhood ALL cases (n=50) and non-cancer controls (n=50) frequency-matched to cases by age and sex, recruited from three teaching hospitals in Seoul between 2003 and 2008, were genotyped using Affymetrix SNP Array 6.0 platform. ALL risks were estimated as odds ratios (ORs) and 95% confidence intervals (CIs) adjusted for age and birth weight. The false discovery rate (FDR) was used for adjusting multiple tests. Ofthese 1 million SNPs, six SNPs in 4 genes (HAO1 rs6140264, EPB41L2 rs9388856, rs9388857, rs1360756, C2orf3 12105972, MAN2A1 rs3776932) were strongly associated with childhood ALL risk (P(dominant)children identified a few genetic variations as potential susceptibility markers for ALL, warranting further replication studiesamong various ethnic groups.#CI- Copyright (c) 2010 Elsevier Ltd. ALL rights reserved.