title: Prevalence of aberrant methylation of p14ARF over p16INK4a in some human primary tumors.
abstract: The INK4a/ARF locus encodes two unrelated tumor suppressor proteins, p16INK4a and p14ARF, which participate in the two main cell-cycle control pathways, p16-Rb and p14-p53. Methylation of CpG promoter islands has been described as a mechanism of gene silencing. Exon 1 of the p16INK4a gene and the p14ARF promoter gene reside within CpG islands. Therefore, both can become methylated de novo and silenced. It has recently been proposed that the methylation changes in certain genes could be used as molecular markers for the detection of almost all forms of human cancer. Here, we analyzed concomitantly in each tumor sample and normal tissue the methylation status of p16INK4a and p14ARF by methylation-specific PCR (MSP) in 100 breast, 95 colon and 27 bladder carcinomas. A series of clinicopathological parameter were obtained from the medical records of the patients, p14ARF showed a higher rate of hypermethylation than p16INK4a in all three tumor types. p16INK4a and p14ARF aberrant methylation was significantly correlated with poor prognosis clinicopathological parameters of the three tumor types. We conclude that both p16INKa and p14ARF hypermethylation may be involved in breast, colon and bladder carcinogenesis, with special emphasis on the role of the lesser studied p14ARF gene, and that tumors with aberrant methylation in the two genes were associated with worse prognosis.
authors.affiliation: Department of Medical Oncology, Hospital Universitario Puerta de Hierro, C/San Martin de Porres 4, E-28035, Madrid, Spain.
authors.forename: Gemma
authors.initials: G
authors.lastname: Dominguez
authors.forename: Javier
authors.initials: J
authors.lastname: Silva
authors.forename: Jose M
authors.initials: JM
authors.lastname: Garcia
authors.forename: Jose M
authors.initials: JM
authors.lastname: Silva
authors.forename: Rufo
authors.initials: R
authors.lastname: Rodriguez
authors.forename: Concepción
authors.initials: C
authors.lastname: Muñoz
authors.forename: Ignacio
authors.initials: I
authors.lastname: Chacón
authors.forename: Rosario
authors.initials: R
authors.lastname: Sanchez
authors.forename: Joaquin
authors.initials: J
authors.lastname: Carballido
authors.forename: Antonio
authors.initials: A
authors.lastname: Colás
authors.forename: Pilar
authors.initials: P
authors.lastname: España
authors.forename: Félix
authors.initials: F
authors.lastname: Bonilla
mesh_terms: D001943:Breast Neoplasms / Q000235:genetics; D002277:Carcinoma / Q000235:genetics; D003110:Colonic Neoplasms / Q000235:genetics; D019941:Cyclin-Dependent Kinase Inhibitor p16 / Q000235:genetics*; D019175:DNA Methylation; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009369:Neoplasms / Q000235:genetics*; D011379:Prognosis; D011401:Promoter Regions, Genetic; D025803:Tumor Suppressor Protein p14ARF / Q000235:genetics*; D001749:Urinary Bladder Neoplasms / Q000235:genetics
chemical_list: D019941:Cyclin-Dependent Kinase Inhibitor p16; D025803:Tumor Suppressor Protein p14ARF