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  • 1
    In: Genes, Chromosomes and Cancer, Wiley, Vol. 53, No. 7 ( 2014-07), p. 537-548
    Abstract: Formalin fixation and embedding of clinical tissue samples in paraffin is a common method for archiving biological material. These samples are often well annotated and provide an invaluable resource for research. However, this process of fixation and storage of tissue leads to DNA damage and fragmentation. The use of DNA from formalin fixed, paraffin‐embedded (FFPE) tissue to interrogate methylation levels on a genome‐wide scale can pose challenges. We compared fresh and matched FFPE tissue DNA samples using the Illumina Infinium HD Human Methylation 450K BeadChip platform with a companion application for repair and “restoration” of DNA from FFPE tissue. Our results showed good correlation between fresh and FFPE sample data. FFPE DNA captured 99% of the CpG sites on the array on average. Significant cancer subgroups based on the CpG island methylator phenotype (CIMP) were clearly distinguished for both fresh and FFPE sample sets with cluster and scaling analysis. The DNA methylation status for the five standard CIMP panel genes which was evaluated for all samples by the MethyLight assay was correctly assigned in both fresh and FFPE samples by the array data. We conclude that the “restoration” method followed by assay on the Infinium HD Human Methylation 450K microarray can produce good quality data for DNA from FFPE samples. © 2014 Wiley Periodicals, Inc.
    Type of Medium: Online Resource
    ISSN: 1045-2257 , 1098-2264
    URL: Issue
    Language: English
    Publisher: Wiley
    Publication Date: 2014
    detail.hit.zdb_id: 1018988-9
    detail.hit.zdb_id: 1492641-6
    SSG: 12
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  • 2
    In: Histopathology, Wiley, Vol. 68, No. 4 ( 2016-03), p. 578-587
    Abstract: Most colorectal polyps are classified readily, but a subset of tubulovillous adenomas (TVA) with prominent serrated architecture causes diagnostic confusion. We aimed to (i) identify histological features that separate serrated TVAs from both conventional TVAs and traditional serrated adenomas (TSA) and (ii) perform a clinicopathological and molecular analysis to determine if the serrated TVA has unique features. Methods and results We collected 48 serrated TVAs, 50 conventional TVAs and 66 BRAF wild‐type TSAs for analysis. For each polyp we performed a clinicopathological assessment, BRAF and KRAS mutation profiling, cytosine–phosphate–guanosine (CpG) island methylator phenotype status, MGMT methylation and immunohistochemical assessment of seven markers [MutL homologue 1 (MLH1), p16, p53, β‐catenin, Ki67, CK7 and CK20]. We found that serrated TVAs can be diagnosed reliably, and have features distinct from both conventional TVAs and TSAs. Compared to conventional TVAs, serrated TVAs are larger, more often proximal, more histologically advanced, show more CpG island methylation and more frequent KRAS mutation. Compared to TSAs they are more often proximal, show less CpG island methylation, more frequent MGMT methylation and more frequent nuclear staining for β‐catenin. Conclusions The serrated TVA can be diagnosed reliably and has unique features. It represents a precursor of KRAS mutated, microsatellite stable colorectal carcinoma.
    Type of Medium: Online Resource
    ISSN: 0309-0167 , 1365-2559
    URL: Issue
    RVK:
    Language: English
    Publisher: Wiley
    Publication Date: 2016
    detail.hit.zdb_id: 2006447-0
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