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Promoter hypermethylation profile of kidney cancer.

Publication ,  Journal Article
Dulaimi, E; Ibanez de Caceres, I; Uzzo, RG; Al-Saleem, T; Greenberg, RE; Polascik, TJ; Babb, JS; Grizzle, WE; Cairns, P
Published in: Clin Cancer Res
June 15, 2004

PURPOSE: Promoter hypermethylation is an important mechanism of inactivation of tumor suppressor genes in cancer cells. Kidney tumors are heterogeneous in their histology, genetics, and clinical behavior. To gain insight into the role of epigenetic silencing of tumor suppressor and cancer genes in kidney tumorigenesis, we determined a hypermethylation profile of kidney cancer. EXPERIMENTAL DESIGN: We examined the promoter methylation status of 10 biologically significant tumor suppressor and cancer genes in 100 kidney tumors (50 clear cell, 20 papillary, 6 chromophobe, 5 collecting duct, 5 renal cell unclassified, 7 oncocytoma, 6 transitional cell carcinomas of the renal pelvis, and 1 Wilms' tumor) by methylation-specific PCR. The hypermethylation profile was examined with regard to clinicopathological characteristics of the kidney cancer patients. RESULTS: Hypermethylation of one or more genes was found in 93 (93%) of 100 tumors. A total of 33% of kidney tumors had one gene, 35% two genes, 14% three genes, and 11% four or more genes hypermethylated. The frequency of hypermethylation of the 10 genes in the 100 tumor DNAs was VHL 8% (all clear cell), p16(INK4a) 10%, p14(ARF) 17%, APC 14%, MGMT 7%, GSTP1 12%, RARbeta2 12%, RASSF1A 45%, E-cadherin 11%, and Timp-3 58%. Hypermethylation was observed in all of the histological cell types and grades and stages examined. No hypermethylation was observed in specimens of normal kidney or ureteral tissue from 15 patients. Hypermethylation of VHL was specific to clear cell tumors. RASSF1A methylation was detected at a significantly higher frequency in papillary renal cell tumors and in high-grade tumors of all cell types. MGMT methylation was more frequent in nonsmokers. Simultaneous methylation of five or more genes was observed in 3 (3%) of 100 tumors and may indicate a methylator phenotype in kidney cancer. In addition, the CpG island in the promoter of the fumarate hydratase (FH) tumor suppressor gene was bisulfite sequenced and was found to be unmethylated in 15 papillary renal tumors. CONCLUSIONS: Promoter hypermethylation is common, can occur relatively early, may disrupt critical pathways, and, thus, likely plays an important role in kidney tumorigenesis. A hypermethylation profile may be useful in predicting a patient's clinical outcome and provide molecular markers for diagnostic and prognostic approaches to kidney cancer.

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Published In

Clin Cancer Res

DOI

ISSN

1078-0432

Publication Date

June 15, 2004

Volume

10

Issue

12 Pt 1

Start / End Page

3972 / 3979

Location

United States

Related Subject Headings

  • Time Factors
  • Sulfites
  • Promoter Regions, Genetic
  • Oncology & Carcinogenesis
  • Neoplasms
  • Neoplasm Metastasis
  • Molecular Sequence Data
  • Middle Aged
  • Male
  • Logistic Models
 

Citation

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Dulaimi, E., Ibanez de Caceres, I., Uzzo, R. G., Al-Saleem, T., Greenberg, R. E., Polascik, T. J., … Cairns, P. (2004). Promoter hypermethylation profile of kidney cancer. Clin Cancer Res, 10(12 Pt 1), 3972–3979. https://doi.org/10.1158/1078-0432.CCR-04-0175
Dulaimi, Essel, Inmaculada Ibanez de Caceres, Robert G. Uzzo, Tahseen Al-Saleem, Richard E. Greenberg, Thomas J. Polascik, James S. Babb, William E. Grizzle, and Paul Cairns. “Promoter hypermethylation profile of kidney cancer.Clin Cancer Res 10, no. 12 Pt 1 (June 15, 2004): 3972–79. https://doi.org/10.1158/1078-0432.CCR-04-0175.
Dulaimi E, Ibanez de Caceres I, Uzzo RG, Al-Saleem T, Greenberg RE, Polascik TJ, et al. Promoter hypermethylation profile of kidney cancer. Clin Cancer Res. 2004 Jun 15;10(12 Pt 1):3972–9.
Dulaimi, Essel, et al. “Promoter hypermethylation profile of kidney cancer.Clin Cancer Res, vol. 10, no. 12 Pt 1, June 2004, pp. 3972–79. Pubmed, doi:10.1158/1078-0432.CCR-04-0175.
Dulaimi E, Ibanez de Caceres I, Uzzo RG, Al-Saleem T, Greenberg RE, Polascik TJ, Babb JS, Grizzle WE, Cairns P. Promoter hypermethylation profile of kidney cancer. Clin Cancer Res. 2004 Jun 15;10(12 Pt 1):3972–3979.

Published In

Clin Cancer Res

DOI

ISSN

1078-0432

Publication Date

June 15, 2004

Volume

10

Issue

12 Pt 1

Start / End Page

3972 / 3979

Location

United States

Related Subject Headings

  • Time Factors
  • Sulfites
  • Promoter Regions, Genetic
  • Oncology & Carcinogenesis
  • Neoplasms
  • Neoplasm Metastasis
  • Molecular Sequence Data
  • Middle Aged
  • Male
  • Logistic Models