title: [Genetic analysis results of patients with a retinoblastoma refractory to systemic chemotherapy].
abstract: OBJECTIVE
  To analyze the genetic alterations identified in the RB1 gene in retinoblastoma patients who do not respond to systemic chemotherapy.
  
  
  METHODS
  A genetic analysis was performed on 115 patients with retinoblastoma, 40 of whom had received systemic chemotherapy, and 29 of them had bilateral disease. Descriptive and retrospective study. Non-responders were considered as patients who are finally enucleated.
  
  
  RESULTS
  Patients with deletion type mutations are those with less preservation of the eyeball (Pearson Chi-square, P=.055). Patients with an impaired nonsense-frameshift type are more likely to preserve the eyeball. Of the 3 patients who had undergone bilateral enucleation, 2 of them had deletions and one missense alteration. Survival analysis (Kaplan-Meier curve) shows that patients with deletion type mutations are more resistance to chemotherapy, are suffering higher rates of enucleation, and for a shorter period of time (log rank [Mantel-Cox] with a significance level of P=.053), which are also associated with increased rate of being bilateral.
  
  
  CONCLUSIONS
  Patients with a genotype show increased resistance to chemotherapy should be evaluated more closely and treated with various therapeutic weapons early. Patients that have deletions in the RB1 gene are at increased risk of chemoresistance. It is likely that other genetic alterations other than RB1 gene may be related to tumor aggressiveness and treatment resistance.
authors: Servicio de Oftalmología, Hospital Manises, Valencia, España. Electronic address: noeruizdelrio@yahoo.es.
authors: N
authors: N
authors: Ruiz del Río
authors: Servicio de Oftalmología Infantil, Hospital Universitario La Paz, Madrid, España.
authors: J M
authors: JM
authors: Abelairas Gómez
authors: Instituto de Investigaciones Biomédicas Alberto Sols, Madrid, España.
authors: F J
authors: FJ
authors: Alonso García de la Rosa
authors: Servicio de Oftalmología Infantil, Hospital Universitario La Paz, Madrid, España.
authors: J M
authors: JM
authors: Peralta Calvo
authors: Servicio de Oftalmología, Hospital La Mancha Centro, Ciudad Real, España.
authors: A
authors: A
authors: de las Heras Martín
mesh_terms: D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D004252:DNA Mutational Analysis; D019008:Drug Resistance, Neoplasm; D015353:Eye Enucleation; D005260:Female; D005838:Genotype; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D009154:Mutation; D009361:Neoplasm Invasiveness; D009378:Neoplasms, Multiple Primary / Q000188:drug therapy / Q000235:genetics / Q000601:surgery; D016016:Proportional Hazards Models; D019572:Retinal Neoplasms / Q000188:drug therapy / Q000235:genetics* / Q000601:surgery; D012175:Retinoblastoma / Q000188:drug therapy / Q000235:genetics* / Q000601:surgery; D056286:Retinoblastoma Binding Proteins / Q000235:genetics*; D012189:Retrospective Studies; D017384:Sequence Deletion; D044767:Ubiquitin-Protein Ligases / Q000235:genetics*
chemical_list: C000606393:RB1 protein, human; D056286:Retinoblastoma Binding Proteins; D044767:Ubiquitin-Protein Ligases
keywords: Chemoresistance; Gen RB1; Genética; Quimiorresistencia; Quimioterapia sistémica; Retinoblastoma; Systemic chemotherapy