دورية أكاديمية

The First Neuroendocrine Tumor Methylome Using Methylation-Specific Immunoprecipitation Followed by Second Generation Sequencing -- MeDIP-seq.

التفاصيل البيبلوغرافية
العنوان: The First Neuroendocrine Tumor Methylome Using Methylation-Specific Immunoprecipitation Followed by Second Generation Sequencing -- MeDIP-seq.
المؤلفون: Thirlwell, C., Sasmaz, S., Dibra, H., Feber, A., Butcher, L., Meyer, T., Davidson, B., Caplin, M., Wilson, G., Beck, S.
المصدر: Neuroendocrinology; Jul2012 Supplement, Vol. 96, p14-14, 1/4p
مصطلحات موضوعية: NEUROENDOCRINE tumors, CARCINOID, LIVER cancer, PANCREATIC cancer, METHYLATION
مستخلص: Introduction: Recently, the first cancer methylomes have been created which identified differential methylation at CpG islandshores (2kb upstream of CpG islands) to be of particular importance in the tumourigenic process. Aim(s): To produce the first methylome in NETs using second generation sequencing -- enabling coverage of >20 million CpGs located throughout the genome in coding and non-coding regions. Materials and methods: Nine fresh frozen sporadic pancreatic NET liver metastases (three low, intermediate and high grade) and two normal pancreatic paraffin-embedded tissue samples underwent whole-genome CpG methylation-specific immunoprecipitation followed by sequencing on the Illumina GAIIx sequencer (MeDIP-seq). MeDIP-seq data were processed using our novel analysis pipeline MEDUSA (Methylated DNA Utility for Sequence Analysis). Results: Between 21 and 50 million QC approved unique reads were mapped per sample. Using a FDR of 0.01 (1%), DMRs were identified between normal pancreatic tissue and low (3546), intermediate (17542) and high (11219) grade pancreatic NETs and also between low and intermediate (5021), low and high (5292) and intermediate and high (6815) grade pancreatic NETs. Conclusion: This is the first MeDIP-seq analysis to be performed in NETs. Increasing global hypomethylation was observed between low to high grades of tumor. Gene ontology analysis identified pathways occurring in malignant glioma and nervous system cancer to be implicated in the development of intermediate and high grade tumors. [ABSTRACT FROM AUTHOR]
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