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  • Morreau, Hans  (3)
  • Oosting, Jan  (3)
  • 1
    Online-Ressource
    Online-Ressource
    Reliable High-Throughput Genotyping and Loss-of-Heterozygosity Detection in Formalin-Fixed, Paraffin-Embedded Tumors Using Single Nucleotide Polymorphism Arrays
    American Association for Cancer Research (AACR) ; 2005
    In:  Cancer Research Vol. 65, No. 22 ( 2005-11-15), p. 10188-10191
    Details
    In: Cancer Research, American Association for Cancer Research (AACR), Vol. 65, No. 22 ( 2005-11-15), p. 10188-10191
    Kurzfassung: Most human cancers show genetic instabilities leading to allelic imbalances, including loss of heterozygosity (LOH). Single nucleotide polymorphism (SNP) arrays can be used to detect LOH. Currently, these arrays require intact genomic DNA as obtained from frozen tissue; however, for most cancer cases, only low-quality DNA from formalin-fixed, paraffin-embedded (FFPE) tissue is available. In this study, we tested Illumina BeadArrays to genotype FFPE tissue and detect LOH/allelic imbalances in matched colorectal tumor and normal tissue. Genotypes were compared between leukocyte and FFPE normal tissue as well as between frozen and FFPE tumor tissue. Identical genotypes and LOH profiles were obtained from normal and tumor isolates. LOH was mainly observed on chromosomes 4, 5q, 12q, 14q, 15q, 17p, 18, and 20p, which are commonly detected regions in colorectal cancer. LOH profiles of the BeadArrays were compared with profiles obtained by Affymetrix GeneChip 10K arrays, showing identical LOH patterns. These data show that genome-wide genotyping of FFPE tissue with the BeadArray gives reliable results and is a powerful technique for LOH analysis.
    Materialart: Online-Ressource
    ISSN: 0008-5472 , 1538-7445
    URL: Article
    DOI: 10.1158/0008-5472.CAN-05-2486
    RVK:
    XA 36000
    RVK:
    XA 10000
    Sprache: Englisch
    Verlag: American Association for Cancer Research (AACR)
    Publikationsdatum: 2005
    ZDB Id: 2036785-5
    ZDB Id: 1432-1
    ZDB Id: 410466-3
    Standort Signatur Einschränkungen Verfügbarkeit
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    Online-Ressource
  • 2
    Online-Ressource
    Online-Ressource
    High-resolution copy number analysis of paraffin-embedded archival tissue using SNP BeadArrays
    Cold Spring Harbor Laboratory ; 2007
    In:  Genome Research Vol. 17, No. 3 ( 2007-03), p. 368-376
    Details
    In: Genome Research, Cold Spring Harbor Laboratory, Vol. 17, No. 3 ( 2007-03), p. 368-376
    Kurzfassung: High-density SNP microarrays provide insight into the genomic events that occur in diseases like cancer through their capability to measure both LOH and genomic copy numbers. Where currently available methods are restricted to the use of fresh frozen tissue, we now describe the design and validation of copy number measurements using the Illumina BeadArray platform and the application of this technique to formalin-fixed, paraffin-embedded (FFPE) tissue. In fresh frozen tissue from a set of colorectal tumors with numerous chromosomal aberrations, our method measures copy number patterns that are comparable to values from established platforms, like Affymetrix GeneChip and BAC array-CGH. Moreover, paired comparisons of fresh frozen and FFPE tissues showed nearly identical patterns of genomic change. We conclude that this method enables the use of paraffin-embedded material for research into both LOH and numerical chromosomal abnormalities. These findings make the large pathological archives available for genomic analysis, which could be especially relevant for hereditary disease where fresh material from affected relatives is rarely available.
    Materialart: Online-Ressource
    ISSN: 1088-9051
    URL: Article
    DOI: 10.1101/gr.5686107
    RVK:
    XA 10000
    Sprache: Englisch
    Verlag: Cold Spring Harbor Laboratory
    Publikationsdatum: 2007
    ZDB Id: 1483456-X
    SSG: 12
    Standort Signatur Einschränkungen Verfügbarkeit
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    Online-Ressource
  • 3
    Online-Ressource
    Online-Ressource
    Progression and Tumor Heterogeneity Analysis in Early Rectal Cancer
    American Association for Cancer Research (AACR) ; 2008
    In:  Clinical Cancer Research Vol. 14, No. 3 ( 2008-02-01), p. 772-781
    Details
    In: Clinical Cancer Research, American Association for Cancer Research (AACR), Vol. 14, No. 3 ( 2008-02-01), p. 772-781
    Kurzfassung: Purpose: Adequate preoperative staging of large sessile rectal tumors requires identifying adenomas that already contain an invasive focus, specifically those that are growing in or beyond the submucosa. We systematically compared chromosomal instability patterns in adenoma and carcinoma fractions of the same lesion to assess specific steps in rectal tumor progression. Experimental Design: We analyzed 36 formalin-fixed, paraffin-embedded tumors. Both the adenoma and carcinoma fractions were typed with single nucleotide polymorphism arrays and compared with 21 previously described pure adenomas. Eighteen cases were included in an intratumor heterogeneity analysis. Results: Five specific “malignant” events (gain of 8q, 13q, and 20q and loss of 17p and 18q) and aberrant staining for p53 and SMAD4 were all increased in the adenoma fractions of carcinoma cases compared with pure adenomas. Paired analysis revealed that 31% of the samples had an equal amount of malignant aberrations in their adenoma and carcinoma fractions, whereas 25% had one and 33% had two or more extra malignant events in the carcinoma fraction. Analysis of three core biopsies per patient showed a large degree of intratumor heterogeneity. However, the number of malignant aberrations in the biopsy with the most aberrations per tumor correlated with the corresponding adenoma or carcinoma fraction (r = 0.807; P & lt; 0.001). Conclusion: Five specific chromosomal aberrations, combined with immunohistochemistry for p53 and SMAD4, can predict possible progression of sessile rectal adenomas to early rectal cancer and can, after validation studies, be added to preoperative staging. Preferably, three biopsies should be taken from each tumor to address intratumor heterogeneity.
    Materialart: Online-Ressource
    ISSN: 1078-0432 , 1557-3265
    URL: Article
    DOI: 10.1158/1078-0432.CCR-07-2052
    RVK:
    XA 36791
    Sprache: Englisch
    Verlag: American Association for Cancer Research (AACR)
    Publikationsdatum: 2008
    ZDB Id: 1225457-5
    ZDB Id: 2036787-9
    Standort Signatur Einschränkungen Verfügbarkeit
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    Online-Ressource
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