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Frequent IGF2/H19 domain epigenetic alterations and elevated IGF2 expression in epithelial ovarian cancer.

Publication ,  Journal Article
Murphy, SK; Huang, Z; Wen, Y; Spillman, MA; Whitaker, RS; Simel, LR; Nichols, TD; Marks, JR; Berchuck, A
Published in: Mol Cancer Res
April 2006

Overexpression of the imprinted insulin-like growth factor-II (IGF2) is a prominent characteristic of gynecologic malignancies. The purpose of this study was to determine whether IGF2 loss of imprinting (LOI), aberrant H19 expression, and/or epigenetic deregulation of the IGF2/H19 imprinted domain contributes to elevated IGF2 expression in serous epithelial ovarian tumors. IGF2 LOI was observed in 5 of 23 informative serous epithelial ovarian cancers, but this did not correlate with elevated expression of IGF2 H19 RNA expression levels were also found not to correlate with IGF2 transcript levels. However, we identified positive correlations between elevated IGF2 expression and hypermethylation of CCCTC transcription factor binding sites 1 and 6 at the H19 proximal imprint center (P = 0.05 and 0.02, respectively). Hypermethylation of CCCTC transcription factor sites 1 and 6 was observed more frequently in cancer DNA compared with lymphocyte DNA obtained from women without malignancy (P < 0.0001 for both sites 1 and 6). Ovarian cancers were also more likely to exhibit maternal allele-specific hypomethylation upstream of the imprinted IGF2 promoters when compared with normal lymphocyte DNA (P = 0.004). This is the same region shown previously to be hypomethylated in colon cancers with IGF2 LOI, but this was not associated with LOI in ovarian cancers. Elevated IGF2 expression is a frequent event in serous ovarian cancer and this occurs in the absence of IGF2 LOI. These data indicate that the epigenetic changes observed in these cancers at the imprint center may contribute to IGF2 overexpression in a novel mechanistic manner.

Duke Scholars

Published In

Mol Cancer Res

DOI

ISSN

1541-7786

Publication Date

April 2006

Volume

4

Issue

4

Start / End Page

283 / 292

Location

United States

Related Subject Headings

  • Transcriptional Activation
  • Repressor Proteins
  • RNA, Untranslated
  • RNA, Long Noncoding
  • Protein Structure, Tertiary
  • Ovarian Neoplasms
  • Oncology & Carcinogenesis
  • Insulin-Like Growth Factor II
  • Humans
  • Genomic Imprinting
 

Citation

APA
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MLA
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Murphy, S. K., Huang, Z., Wen, Y., Spillman, M. A., Whitaker, R. S., Simel, L. R., … Berchuck, A. (2006). Frequent IGF2/H19 domain epigenetic alterations and elevated IGF2 expression in epithelial ovarian cancer. Mol Cancer Res, 4(4), 283–292. https://doi.org/10.1158/1541-7786.MCR-05-0138
Murphy, Susan K., Zhiqing Huang, Yaqing Wen, Monique A. Spillman, Regina S. Whitaker, Lauren R. Simel, Teresa D. Nichols, Jeffrey R. Marks, and Andrew Berchuck. “Frequent IGF2/H19 domain epigenetic alterations and elevated IGF2 expression in epithelial ovarian cancer.Mol Cancer Res 4, no. 4 (April 2006): 283–92. https://doi.org/10.1158/1541-7786.MCR-05-0138.
Murphy SK, Huang Z, Wen Y, Spillman MA, Whitaker RS, Simel LR, et al. Frequent IGF2/H19 domain epigenetic alterations and elevated IGF2 expression in epithelial ovarian cancer. Mol Cancer Res. 2006 Apr;4(4):283–92.
Murphy, Susan K., et al. “Frequent IGF2/H19 domain epigenetic alterations and elevated IGF2 expression in epithelial ovarian cancer.Mol Cancer Res, vol. 4, no. 4, Apr. 2006, pp. 283–92. Pubmed, doi:10.1158/1541-7786.MCR-05-0138.
Murphy SK, Huang Z, Wen Y, Spillman MA, Whitaker RS, Simel LR, Nichols TD, Marks JR, Berchuck A. Frequent IGF2/H19 domain epigenetic alterations and elevated IGF2 expression in epithelial ovarian cancer. Mol Cancer Res. 2006 Apr;4(4):283–292.

Published In

Mol Cancer Res

DOI

ISSN

1541-7786

Publication Date

April 2006

Volume

4

Issue

4

Start / End Page

283 / 292

Location

United States

Related Subject Headings

  • Transcriptional Activation
  • Repressor Proteins
  • RNA, Untranslated
  • RNA, Long Noncoding
  • Protein Structure, Tertiary
  • Ovarian Neoplasms
  • Oncology & Carcinogenesis
  • Insulin-Like Growth Factor II
  • Humans
  • Genomic Imprinting