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The importance of 10q status in an outcomes-based comparison between 1p/19q fluorescence in situ hybridization and polymerase chain reaction-based microsatellite loss of heterozygosity analysis of oligodendrogliomas.

ABSTRACT: 1p/19q codeletion is a favorable prognostic marker of oligodendrogliomas. Although fluorescence in situ hybridization (FISH) and microsatellite-based polymerase chain reaction (PCR) for loss of heterozygosity (LOH) are common methods to test for 1p/19q codeletion, it is unclear which test is better at prognostic stratification. This study analyzed outcomes of 111 oligodendrogliomas with both 1p/19q FISH and LOH done at the time of diagnosis. Overall concordance between the 2 assays was 81.1%. In grade III oligodendrogliomas, LOH was better than FISH at survival stratification (p < 0.0001 for LOH vs p = 0.02 for FISH), although increasing the stringency of FISH interpretation criteria improved concordance and prognostic power. Oligodendrogliomas that were 1p/19q-codeleted by FISH but also had 10q LOH were negative for 1p/19q codeletion by PCR analysis in more than 70% of cases, with very poor survival in the grade III subset. Thus, although PCR-based LOH is a better stratifier of 1p/19q status, FISH still has clinical and prognostic utility, especially if 10q data can be incorporated.

SUBMITTER: Horbinski C

PROVIDER: S-EPMC3246063 | biostudies-literature | 2012 Jan

REPOSITORIES: biostudies-literature

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The importance of 10q status in an outcomes-based comparison between 1p/19q fluorescence in situ hybridization and polymerase chain reaction-based microsatellite loss of heterozygosity analysis of oligodendrogliomas.

Horbinski Craig C Nikiforova Marina N MN Hobbs Jonathan J Bortoluzzi Stephanie S Cieply Kathleen K Dacic Sanja S Hamilton Ronald L RL

Journal of neuropathology and experimental neurology 20120101 1

1p/19q codeletion is a favorable prognostic marker of oligodendrogliomas. Although fluorescence in situ hybridization (FISH) and microsatellite-based polymerase chain reaction (PCR) for loss of heterozygosity (LOH) are common methods to test for 1p/19q codeletion, it is unclear which test is better at prognostic stratification. This study analyzed outcomes of 111 oligodendrogliomas with both 1p/19q FISH and LOH done at the time of diagnosis. Overall concordance between the 2 assays was 81.1%. In ...[more]

PMID: 22157622

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Project description:Approximately 50-80% of oligodendrogliomas demonstrate a combined loss of chromosome 1p and 19q. Chromosome 1p/19q deletion, appearing early in tumorigenesis, is associated with improved clinical outcomes, including response to chemotherapy and radiation. Although many hypotheses have been proposed, the molecular mechanisms underlying improved clinical outcomes with 1p/19q deletion in oligodendrogliomas have not been characterized fully. To investigate the molecular differences between oligodendrogliomas, we employed an unbiased proteomic approach using microcapillary liquid chromatography mass spectrometry, along with a quantitative technique called isotope-coded affinity tags, on patient samples of grade II oligodendrogliomas. Following conventional biochemical separation of pooled tumor tissue from five samples of undeleted and 1p/19q deleted grade II oligodendrogliomas into nuclei-, mitochondria-, and cytosol-enriched fractions, relative changes in protein abundance were quantified. Among the 442 total proteins identified, 163 nonredundant proteins displayed significant changes in relative abundance in at least one of the three fractions between oligodendroglioma with and without 1p/19q deletion. Bioinformatic analyses of differentially regulated proteins supported the potential importance of metabolism and invasion/migration to the codeleted phenotype. A subset of altered proteins, including the pro-invasive extracellular matrix protein BCAN, was further validated by Western blotting as candidate markers for the more aggressive undeleted phenotype. These studies demonstrate the utility of proteomic analysis to identify candidate biological motifs and molecular mechanisms that drive differential malignancy related to 1p19q phenotypes. Future analysis of larger patient samples are warranted to further refine biomarker panels to predict biological behavior and assist in the identification of deleted gene products that define the 1p/19q phenotype.

Dataset Information

The importance of 10q status in an outcomes-based comparison between 1p/19q fluorescence in situ hybridization and polymerase chain reaction-based microsatellite loss of heterozygosity analysis of oligodendrogliomas.

Publications

The importance of 10q status in an outcomes-based comparison between 1p/19q fluorescence in situ hybridization and polymerase chain reaction-based microsatellite loss of heterozygosity analysis of oligodendrogliomas.

Similar Datasets

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