Promoter hypermethylation of multiple genes in astrocytic gliomas

  • Authors:
    • Pilar Gonzalez-Gomez
    • M. Josefa Bello
    • Dolores Arjona
    • Jesus Lomas
    • M. Eva Alonso
    • Jose M. De Campos
    • Jesus Vaquero
    • Alberto Isla
    • Manuel Gutierrez
    • Juan A. Rey
  • View Affiliations

  • Published online on: March 1, 2003     https://doi.org/10.3892/ijo.22.3.601
  • Pages: 601-608
Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )
Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )


Abstract

Promoter hypermethylation represents a primary mechanism in the inactivation of tumor suppressor genes during tumorigenesis. To determine the frequency and timing of hypermethylation during carcinogenesis of astrocytic tumors, we analysed promoter methylation status of ten tumor-associated genes (MGMT, GSTP1, DAPK, p14ARF, THBS1, TIMP-3, p73, p16INK4A, RB1 and TP53) in a series of 88 astrocytic gliomas, including 24 diffuse astrocytomas; 21 anaplastic astrocytomas, and 43 glioblastomas (33 primary and 10 secondary), as well as two non-neoplastic brain samples, by methylation-specific PCR. Aberrant CpG island methylation was detected in all ten genes analysed, and all but one sample displayed anomalies in at least one gene. The methylation index (number methylated genes/total genes analysed) was 0.3, 0.38, 0.33 and 0.29 for diffuse astrocytomas, anaplastic astrocytomas and secondary and primary glioblastomas, respectively. Some differences may be established regarding the methylation profiles of specific genes and tumor types: MGMT, THBS1, TIMP-3, and p16INK4A appear hypermethylated in low-grade tumors (at least in 45% of cases), whereas GSTP1, DAPK, and p14ARF are mostly changed in 15-50% of the higher grade forms versus <10% in low-grade tumors. Some variation also exists regarding the methylation values for p73 and RB1 (10-40% of cases) among all groups. TP53 presented hypermethylation rates <10% in all tumor subtypes. Our findings thus suggest that methylation represents a common mechanism that contributes to inactivating cancer-related genes in astrocytic neoplasms. This epigenetic change is, in general, an early event in the development of astrocytic neoplasms but this gene silencing mechanism may also appear as a late event involving some loci.

Related Articles

Journal Cover

March 2003
Volume 22 Issue 3

Print ISSN: 1019-6439
Online ISSN:1791-2423

Sign up for eToc alerts

Recommend to Library

Copy and paste a formatted citation
x
Spandidos Publications style
Gonzalez-Gomez P, Bello MJ, Arjona D, Lomas J, Alonso ME, De Campos JM, Vaquero J, Isla A, Gutierrez M, Rey JA, Rey JA, et al: Promoter hypermethylation of multiple genes in astrocytic gliomas. Int J Oncol 22: 601-608, 2003.
APA
Gonzalez-Gomez, P., Bello, M.J., Arjona, D., Lomas, J., Alonso, M.E., De Campos, J.M. ... Rey, J.A. (2003). Promoter hypermethylation of multiple genes in astrocytic gliomas. International Journal of Oncology, 22, 601-608. https://doi.org/10.3892/ijo.22.3.601
MLA
Gonzalez-Gomez, P., Bello, M. J., Arjona, D., Lomas, J., Alonso, M. E., De Campos, J. M., Vaquero, J., Isla, A., Gutierrez, M., Rey, J. A."Promoter hypermethylation of multiple genes in astrocytic gliomas". International Journal of Oncology 22.3 (2003): 601-608.
Chicago
Gonzalez-Gomez, P., Bello, M. J., Arjona, D., Lomas, J., Alonso, M. E., De Campos, J. M., Vaquero, J., Isla, A., Gutierrez, M., Rey, J. A."Promoter hypermethylation of multiple genes in astrocytic gliomas". International Journal of Oncology 22, no. 3 (2003): 601-608. https://doi.org/10.3892/ijo.22.3.601