Anti-FOXL1 monoclonal antibody, clone 3D3

BACKGROUND: DNA methylation is a fundamental epigenetic event associated with physiologic and pathologic conditions, including cancer. Hypermethylation of CpG islands at active gene promoters leads to transcriptional repression, whereas hypomethylation is associated with gene overexpression. The aim of this study was to identify genes in adenoid cystic carcinoma (ACC) of salivary gland strongly deregulated by epigenetic CpG island methylation, to validate selected genes by conventional techniques, and to correlate the findings with clinicopathologic factors. METHODS: The authors analyzed 16 matched normal and tumor tissues for aberrant DNA methylation using the methylated CpG island amplification and microarray method and the pyrosequencing technique. RESULTS: Microarray analysis showed hypomethylation in 7 and hypermethylation in 32 CpG islands. Hypomethylation was identified in CpG islands near FBXO17 PHKG1, LOXL1, DOCK1, and PARVG. Hypermethylation was identified near genes encoding predominantly transcription factors (EN1, FOXE1, GBX2, FOXL1, TBX4, MEIS1, LBX2, NR2F2, POU3F3, IRX3, TFAP2C, NKX2-4, PITX1, NKX2-5), and 13 genes with different functions (MT1H, EPHX3, AQPEP, BCL2L11, SLC35D3, S1PR5, PNLIPRP1, CLIC6, RASAL, XRN2, GSTM5, FNDC1, INSRR). Four CpG islands by EN1, FOXE1, TBX4, and PITX1 were validated by pyrosequencing. CONCLUSIONS: The highly methylated genes in tumor versus normal tissue are linked to developmental, apoptotic, and other fundamental cellular pathways, suggesting that down-regulation of these genes is associated with ACC development and progression. With EN1 hypermethylation showing potential as a possible biomarker for ACC in salivary gland, the biological and therapeutic implications of these findings require further preclinical investigations. Cancer 2011;117:2898-909. (C) 2077 American Cancer Society.

Bone mineral density (BMD) is a heritable complex trait used in the clinical diagnosis of osteoporosis and the assessment of fracture risk. We performed meta-analysis of five genome-wide association studies of femoral neck and lumbar spine BMD in 19,195 subjects of Northern European descent. We identified 20 BMD loci that reached genome-wide significance (GWS; P < 5 x 10(-8)), of which 13 map to regions not previously associated with this trait: 1p31.3 (GPR177), 2p21 (SPTBN1), 3p22 (CTNNB1), 4q21.1 (MEPE), 5q14 (MEF2C), 7p14 (STARD3NL), 7q21.3 (FLJ42280), 11p11.2 (LRP4, ARHGAP1, F2), 11p14.1 (DCDC5), 11p15 (SOX6), 16q24 (FOXL1), 17q21 (HDAC5) and 17q12 (CRHR1). The meta-analysis also confirmed at GWS level seven known BMD loci on 1p36 (ZBTB40), 6q25 (ESR1), 8q24 (TNFRSF11B), 11q13.4 (LRP5), 12q13 (SP7), 13q14 (TNFSF11) and 18q21 (TNFRSF11A). The many SNPs associated with BMD map to genes in signaling pathways with relevance to bone metabolism and highlight the complex genetic architecture that underlies osteoporosis and variation in BMD.