Promoter methylation status of multiple genes in brain metastases of solid tumors

  • Authors:
    • Pilar Gonzalez-Gomez
    • M. Josefa Bello
    • M. Eva Alonso
    • Cinthia Amiñoso
    • Isabel Lopez-Marin
    • Jose M. De Campos
    • Alberto Isla
    • Manuel Gutierrez
    • Juan A. Rey
  • View Affiliations

  • Published online on: January 1, 2004     https://doi.org/10.3892/ijmm.13.1.93
  • Pages: 93-98
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Abstract

The aberrant methylation of the CpG island promoter regions acquired by tumor cells is one mechanism for loss of gene function. The high methylation rate for RB1 and death-associated protein-kinase gene (DAP-kinase) (60 and 90%, respectively) previously found in brain metastases suggests this mechanism could be non-randomly associated to tumor progression and metastasis. Thus, in addition to these two genes, we determined the methylation status of the genes p16INK4a, glutathione S-transferase P1 (GSTP1), O6-methylguanine DNA methyltransferase (MGMT), thrombospondin-1 (THBS1), p14ARF, TP53, p73, and tissue inhibitor of metalloproteinase 3 (TIMP-3), in 18 brain metastases of solid tumors, with methylation specific PCR. The metastases were derived from malignant melanoma (three cases), lung carcinoma (six cases), breast carcinoma (three cases), ovarian carcinoma (two cases) and one each from colon, kidney, bladder and undifferentiated carcinoma. We detected methylation levels in the tumor samples of 83% in p16INK4a, 72% in DAP-kinase, 56% in THBS1, 50% in RB1, 39% in MGMT, 33% in GSTP1 and p14ARF each, 22% in p73 and TIMP-3 each, and 11% in TP53. The methylation index (number of genes methylated/number of genes tested) varied between 0.1 and 0.6, with an average of 0.42, indicating that a high grade of gene methylation accumulates parallel to the tumor metastasis process. Our data suggest an important role for gene methylation in the development of brain metastases, primarily involving epigenetic silencing of DAP-kinase, THBS1 and the cell-cycle regulators RB1/p16INK4a.

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January 2004
Volume 13 Issue 1

Print ISSN: 1107-3756
Online ISSN:1791-244X

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Spandidos Publications style
Gonzalez-Gomez P, Bello MJ, Alonso ME, Amiñoso C, Lopez-Marin I, De Campos JM, Isla A, Gutierrez M and Rey JA: Promoter methylation status of multiple genes in brain metastases of solid tumors. Int J Mol Med 13: 93-98, 2004.
APA
Gonzalez-Gomez, P., Bello, M.J., Alonso, M.E., Amiñoso, C., Lopez-Marin, I., De Campos, J.M. ... Rey, J.A. (2004). Promoter methylation status of multiple genes in brain metastases of solid tumors. International Journal of Molecular Medicine, 13, 93-98. https://doi.org/10.3892/ijmm.13.1.93
MLA
Gonzalez-Gomez, P., Bello, M. J., Alonso, M. E., Amiñoso, C., Lopez-Marin, I., De Campos, J. M., Isla, A., Gutierrez, M., Rey, J. A."Promoter methylation status of multiple genes in brain metastases of solid tumors". International Journal of Molecular Medicine 13.1 (2004): 93-98.
Chicago
Gonzalez-Gomez, P., Bello, M. J., Alonso, M. E., Amiñoso, C., Lopez-Marin, I., De Campos, J. M., Isla, A., Gutierrez, M., Rey, J. A."Promoter methylation status of multiple genes in brain metastases of solid tumors". International Journal of Molecular Medicine 13, no. 1 (2004): 93-98. https://doi.org/10.3892/ijmm.13.1.93