Unknown,Transcriptomics,Genomics,Proteomics

Dataset Information

DNA methylome analysis in infants from The Gambia / Aflatoxin / Seasonality study

ABSTRACT: Genome wide DNA methylation profiling in infant's blood from a mother/child cohort in The Gambia. The main variables of the analyses were the intra-uterine exposure to aflatoxin B1 (AFB1) and the season of conception. The Illumina Infinium HumanMethylation 450k Beadchip was used to obtain DNA methylation profiles across approximately 450,000 CpGs in whole peripheral blood obtained at 3-6 months of age. A total of 124 samples were analysed, including 3 technical replicates. Bisulphite converted DNA from the 124 samples were hybridised to the Illumina Infinium HumanMethylation 450k Beadchip

ORGANISM(S): Homo sapiens

SUBMITTER: Hector Hernandez-Vargas

PROVIDER: E-GEOD-59592 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Publications

Exposure to aflatoxin B1 in utero is associated with DNA methylation in white blood cells of infants in The Gambia.

Hernandez-Vargas Hector H Castelino Jovita J Silver Matt J MJ Dominguez-Salas Paula P Cros Marie-Pierre MP Durand Geoffroy G Le Calvez-Kelm Florence F Prentice Andrew M AM Wild Christopher P CP Moore Sophie E SE Hennig Branwen J BJ Herceg Zdenko Z Gong Yun Yun YY Routledge Michael N MN

International journal of epidemiology 20150407 4

<h4>Background</h4>Exposure to environmental toxins during embryonic development may lead to epigenetic changes that influence disease risk in later life. Aflatoxin is a contaminant of staple foods in sub-Saharan Africa, is a known human liver carcinogen and has been associated with stunting in infants.<h4>Methods</h4>We have measured aflatoxin exposure in 115 pregnant women in The Gambia and examined the DNA methylation status of white blood cells from their infants at 2-8 months old (mean 3.6 ...[more]

PMID: 25855716

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Project description:Intra-individual tumoral heterogeneity (ITH) is a hallmark of solid tumors and impedes accurate genomic diagnosis and selection of proper therapy. The purpose of this study was to identify ITH of ovarian serous adenocarcinomas (OSAs) and to determine the utility of ascitic cancer cells as a resource for mutation profiling in spite of ITH. We performed whole-exome sequencing, copy number profiling, and DNA methylation profiling of four OSA genomes using multiregional biopsies from 13 intraovarian lesions, 12 extraovarian tumor lesions (omentum/peritoneum), and ascitic cells. We observed substantial levels of heterogeneity in mutations and copy number alterations (CNAs) of the OSAs. We categorized the mutations into 'common', 'shared' and 'private' according to the regional distribution. Six common, 8 shared, and 24 private mutations were observed in known cancer-related genes,. but common mutations had a higher mutant allele frequency and included TP53 mutations in all four OSAs. Region-specific chromosomal amplifications and deletions involving BRCA1, PIK3CA, and RB1 were also identified. Of note, the mutations detected in ascitic cancer cells represented 92.3-100% of overall somatic mutations in the given case. Phylogenetic analyses of ascitic genomes predicted a polyseeding origin of somatic mutations in ascitic cells. Our results demonstrate that despite ITH, somatic mutations, CNAs, and DNA methylations in both â??commonâ?? category and cancer-related genes were highly conserved in ascitic cells of OSAs, highlighting the clinical relevance of genome analysis of ascitic cells. Ascitic tumor cells may serve as a potential resource to discover somatic mutations of primary OSA with diagnostic and therapeutic relevance. Genome wide DNA methylation profiling of ascitic cells as well as biopsies from ovarian serous adenocarcinomas cases obtained by Illumina Infinium 450k Human DNA methylation Beadchip Bisulphite converted DNA from the 16 samples were hybridized to the Illumina Infinium 450k Human Methylation Beadchip

Dataset Information

DNA methylome analysis in infants from The Gambia / Aflatoxin / Seasonality study

Publications

Exposure to aflatoxin B1 in utero is associated with DNA methylation in white blood cells of infants in The Gambia.

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