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Epigenetic specificity of loss of imprinting of the IGF2 gene in Wilms tumors.

Epigenetic specificity of loss of imprinting of the IGF2 gene in Wilms tumors. Research Abstract Details 

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  • Epigenetic specificity of loss of imprinting of the IGF2 gene in Wilms tumors. Abstract Text:

    hans t bjornssonHans T Bjornsson,lindsey j brownLindsey J Brown,m danielle fallinM Danielle Fallin,michael a rongioneMichael A Rongione,marina bibikovaMarina Bibikova,eliza wickhamEliza Wickham,jian-bing fanJian-Bing Fan,andrew p feinbergAndrew P Feinberg,

    Loss of imprinting (LOI) of the IGF2 gene (which encodes insulin-like growth factor II) is the most common genetic or epigenetic alteration in Wilms tumor; LOI involves aberrant activation of the normally repressed maternally inherited allele. We found previously that LOI of IGF2 occurs in approximately half of all Wilms tumors (i.e., those arising from lineage-committed nephrogenic progenitor cells). We investigated whether LOI of IGF2 is associated with relaxation of imprinting at loci other than IGF2 or with widespread alterations in DNA methylation. We stratified 59 Wilms tumor samples by IGF2 LOI status by use of hot-stop reverse transcription-polymerase chain reaction and/or methylation analysis of the differentially methylated region of the H19 gene and identified 31 samples with and 28 without LOI. We used quantitative allele-specific expression analysis to determine whether six other imprinted genes (i.e., H19, KCNQ1, LIT1, TSSC5, GRB10, and MEG3) had subtle LOI. No statistically significant difference in allele-specific expression between Wilms tumor with or without LOI was found for LIT1, TSSC5, GRB10, and MEG3. For the KCNQ1 gene there was a slight difference between the groups with (37.0%, 95% confidence interval [CI] = 31.8% to 42.2%) and without (27.7%, 95% CI = 21.8% to 33.5%) LOI (P = .02 for F test of group differences in a mixed-effects model). For H19, we also found a slight difference between the groups with (7.5%, 95% CI = 2.4% to 12.7%) and without (2.2%, 95% CI = -3.2% to 7.6%) LOI of IGF2 (P = .15 for F test). In 27 tumor samples, we also used a microarray technique to analyze methylation of 378 genes, 38 of which were suspected or confirmed imprinted genes. We found that statistically significant alterations in only the differentially methylated region of the H19 gene were associated with LOI of IGF2. Thus, epigenetic alterations in Wilms tumors are not widespread, supporting the gene and lineage specificity of LOI of IGF2.

    Epigenetic specificity of loss of imprinting of the IGF2 gene in Wilms tumors. Publishing Authors By Initials

    ht bjornssonHT Bjornsson,lj brownLJ Brown,md fallinMD Fallin,ma rongioneMA Rongione,m bibikovaM Bibikova,e wickhamE Wickham,jb fanJB Fan,ap feinbergAP Feinberg,

    For similar neoplasms: neoplasms by histologic type: neoplasms, complex and mixed: wilms tumor research abstracts see: neoplasms: neoplasms by histologic type: neoplasms, complex and mixed: wilms tumor research

    PUBMED ID PMID:

    MEDLINE DATE:

    Epigenetic specificity of loss of imprinting of the IGF2 gene in Wilms tumors. Journal Published:

    PUBLICATION TYPE: Research Support, N.I.H., Extr

    Journal: Journal of the National Cancer Institute

    VOLUME: 99

    Page Numbers: 1270-3

    Journal Abbreviation: J. Natl. Cancer Inst.

    ISSN: 1460-2105

    DAY: 8

    MONTH: 08

    YEAR: 2007

    Epigenetic specificity of loss of imprinting of the IGF2 gene in Wilms tumors. Information

    Number of References:

    LANGUAGE: eng

    NlmUniqueID: 7503089

    Epigenetic specificity of loss of imprinting of the IGF2 gene in Wilms tumors. Keywords Mesh Terms:

    KEYWORDS: Wilms Tumor

    MESH TERMS: genetics

    Chemical & Substance for Abstract: Epigenetic specificity of loss of imprinting of the IGF2 gene in Wilms tumors. Information

    Substance Name: Insulin-Like Growth Factor II

    Registry Number: 67763-97-7

    Grant and Affiliation Information for Epigenetic specificity of loss of imprinting of the IGF2 gene in Wilms tumors.

    AFFILIATION: Center for Epigenetics, Institute of Basic Biomedical Sciences, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.

    Country: United States

    United States Research PublicationUnited States Research Publication

    AGENCY: United States NCI

    GRANT: CA65145

    ACRONYM: CA

    MEDLINETA: J Natl Cancer Inst

    REFSOURCE:

    DATABASENAME:

    ACCESSION NUMBER:

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