A DNA repeat, NBL2, is hypermethylated in some cancers but hypomethylated in others

Nishiyama, Rie; Qi, Lixin; Tsumagari, Koji; Weissbecker, Karen; Dubeau, Louis; Champagne, Martin A.; Sikka, Suresh C.; Nagai, Hisaki; Ehrlich, Melanie

doi:10.4161/cbt.4.4.1622

Cited by 44 publications

(52 citation statements)

References 44 publications

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“…We analyzed NBL2, a tandem 1.4-kb repeat with a complex sequence. We found recently by Southern blot analysis that NBL2 exhibits either predominant hypermethylation or hypomethylation at HhaI sites in 89% of 18 studied ovarian carcinomas and 84% of 51 Wilms' tumors (12). We also observed hypomethylation at NotI sites in some ovarian carcinomas.…”

Section: Introductionmentioning

confidence: 63%

“…Hairpin genomic sequencing also unambiguously differentiates naturally occurring sequence variation from bisulfite-and PCR-mediated C-to-T conversions at unmethylated cytosines. Our results show that NBL2, which does not seem to be a gene (12), is especially sensitive to multiple diverse DNA methylation changes during oncogenesis, even within the same 0.2-kb region on the same DNA molecule.…”

Section: Introductionmentioning

confidence: 88%

“…This primate-specific sequence (15) is CpG rich (61% C + G; 5.7% CpG). It is present in f200 to 400 copies per haploid human genome, mostly in the vicinity of the centromeres of four of the five acrocentric chromosomes (12), repeat-rich regions for which only little sequence information is available.…”

Section: Introductionmentioning

confidence: 99%

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Both Hypomethylation and Hypermethylation in a 0.2-kb Region of a DNA Repeat in Cancer

Nishiyama

Lacey

et al. 2005

Molecular Cancer Research

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NBL2 is a tandem 1.4-kb DNA repeat, whose hypomethylation in hepatocellular carcinomas was shown previously to be an independent predictor of disease progression. Here, we examined methylation of all cytosine residues in a 0.2-kb subregion of NBL2 in ovarian carcinomas, Wilms' tumors, and diverse control tissues by hairpin-bisulfite PCR. This new genomic sequencing method detects 5-methylcytosine on covalently linked complementary strands of a DNA fragment. All DNA clones from normal somatic tissues displayed symmetrical methylation at seven CpG positions and no methylation or only hemimethylation at two others. Unexpectedly, 56% of cancer DNA clones had decreased methylation at some normally methylated CpG sites as well as increased methylation at one or both of the normally unmethylated sites. All 146 DNA clones from 10 cancers could be distinguished from all 91 somatic control clones by assessing methylation changes at three of these CpG sites. The special involvement of DNA methyltransferase 3B in NBL2 methylation was indicated by analysis of cells from immunodeficiency, centromeric region instability, and facial anomalies syndrome patients who have mutations in the gene encoding DNA methyltransferase 3B. Blot hybridization of 33 cancer DNAs digested with CpG methylation-sensitive enzymes confirmed that NBL2 arrays are unusually susceptible to cancer-linked hypermethylation and hypomethylation, consistent with our novel genomic sequencing findings. The combined Southern blot and genomic sequencing data indicate that some of the cancer-linked alterations in CpG methylation are occurring with considerable sequence specificity. NBL2 is an attractive candidate for an epigenetic cancer marker and for elucidating the nature of epigenetic changes in cancer. (Mol Cancer Res 2005;3(11):617 -26)

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Section: Introductionmentioning

confidence: 63%

Section: Introductionmentioning

confidence: 88%

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Both Hypomethylation and Hypermethylation in a 0.2-kb Region of a DNA Repeat in Cancer

Nishiyama

Lacey

et al. 2005

Molecular Cancer Research

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“…Although the functional importance of decreased methylation is less understood than that of increased modification, both hyper-and hypomethylation of DNA is observed in most cancers (14,23). Genes inactivated by methylation are potential diagnostic markers.…”

Section: Introductionmentioning

confidence: 99%

Analysis of 5‐Methylcytosine in DNA of Breast and Colon Cancer Tissues

et al. 2007

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“…(Fig. 5, Table 1 Human tumours often display genome-wide DNA hypomethylation, which promotes cancer through the effect on chromosomal stability [Gaudet et al 2003;Eden 2003;Yamada et al 2005;Nishiyama et al 2005].…”

Section: Resultsmentioning

confidence: 99%

Molecular Diagnostics of Brain Tumours by Measuring the 5-Methylcytosine Level in Their DNA

Barciszewska¹,

Nowak²,

Gawrońska³

et al. 2011

Brain Tumors - Current and Emerging Therapeutic Strategies

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A DNA repeat, NBL2, is hypermethylated in some cancers but hypomethylated in others

Cited by 44 publications

References 44 publications

Both Hypomethylation and Hypermethylation in a 0.2-kb Region of a DNA Repeat in Cancer

Both Hypomethylation and Hypermethylation in a 0.2-kb Region of a DNA Repeat in Cancer

Analysis of 5‐Methylcytosine in DNA of Breast and Colon Cancer Tissues

Molecular Diagnostics of Brain Tumours by Measuring the 5-Methylcytosine Level in Their DNA

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