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  • Online Resource  (3)
  • Morreau, Hans  (3)
  • Oosting, Jan  (3)
  • 1
    In: Cancer Research, American Association for Cancer Research (AACR), Vol. 65, No. 22 ( 2005-11-15), p. 10188-10191
    Abstract: 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.
    Type of Medium: Online Resource
    ISSN: 0008-5472 , 1538-7445
    RVK:
    RVK:
    Language: English
    Publisher: American Association for Cancer Research (AACR)
    Publication Date: 2005
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    detail.hit.zdb_id: 1432-1
    detail.hit.zdb_id: 410466-3
    Location Call Number Limitation Availability
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  • 2
    In: Clinical Cancer Research, American Association for Cancer Research (AACR), Vol. 14, No. 3 ( 2008-02-01), p. 772-781
    Abstract: 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.
    Type of Medium: Online Resource
    ISSN: 1078-0432 , 1557-3265
    RVK:
    Language: English
    Publisher: American Association for Cancer Research (AACR)
    Publication Date: 2008
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  • 3
    In: Genome Research, Cold Spring Harbor Laboratory, Vol. 17, No. 3 ( 2007-03), p. 368-376
    Abstract: 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.
    Type of Medium: Online Resource
    ISSN: 1088-9051
    RVK:
    Language: English
    Publisher: Cold Spring Harbor Laboratory
    Publication Date: 2007
    detail.hit.zdb_id: 1483456-X
    SSG: 12
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