title: Nonclonal chromosomal aberrations induced by anti-tumoral regimens in childhood cancer: relationship with cancer-related genes and fragile sites.
abstract: Cytogenetic studies were performed on 80 pediatric cancer patients to observe the chromosomal damage, both quantitative and qualitative, induced by chemotherapy. Peripheral blood lymphocytes (PBL) (n = 127) were obtained at diagnosis, during treatment, at remission, and at relapse, and chromosome analysis performed utilizing G-banding standard procedures. The results show a significant increase in the number of altered karyotypes (P = 0.03) in the samples during treatment, returning to values that were similar to those at diagnosis at 2-year remission. Most of the chromosomal aberrations (CA) detected during the chemotherapy regimens were nonclonal, unbalanced (75%), and involved chromosomes 1, 3, 5, 6, 11, 12, 16, and 17 most frequently. There was also a marked increase of CA in samples at relapse with very similar features (type and distribution) to those detected during treatment. There was a good correlation between the chromosomal breakpoints in our series and fragile sites (58%), oncogene (75%), and tumor suppressor gene (33%) loci described in the literature. The results obtained suggest that cytostatic drugs induce a transient increase in chromosome fragility occurring at several cancer-associated breakpoints.
authors.affiliation: Laboratory of Pediatrics, Department of Pediatrics, University of Navarra, Pamplona, Spain.
authors.forename: R
authors.initials: R
authors.lastname: López de Mesa
authors.forename: L
authors.initials: L
authors.lastname: Sierrasesúmaga
authors.forename: M J
authors.initials: MJ
authors.lastname: Calasanz
authors.forename: A L
authors.initials: AL
authors.lastname: López de Cerain
authors.forename: A
authors.initials: A
authors.lastname: Patiño-García
mesh_terms: D000970:Antineoplastic Agents / Q000009:adverse effects* / Q000627:therapeutic use; D016543:Central Nervous System Neoplasms / Q000097:blood / Q000188:drug therapy / Q000235:genetics*; D002648:Child; D002869:Chromosome Aberrations; D019457:Chromosome Breakage; D043283:Chromosome Fragile Sites; D002873:Chromosome Fragility; D006801:Humans; D007621:Karyotyping; D008214:Lymphocytes / Q000187:drug effects / Q000648:ultrastructure; D008223:Lymphoma / Q000097:blood / Q000188:drug therapy / Q000235:genetics*; D012516:Osteosarcoma / Q000097:blood / Q000188:drug therapy / Q000235:genetics*; D012512:Sarcoma, Ewing / Q000097:blood / Q000188:drug therapy / Q000235:genetics*
chemical_list: D000970:Antineoplastic Agents