Nonclonal chromosomal aberrations induced by anti-tumoral regimens in childhood cancer: Relationship with cancer-related genes and fragile sites

Cytogenetic studies rr ere performed on 80 pediatric cancer patients to obs erve 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 sho w a significant increase in the number of altered karyotypes (P = 0.03) in the samples during treatment, returning to values that were similar to thos e at diagnosis at 2-year remission. Most of the chromosomal aberrations (CA ) detected during the chemotherapy regimens rr-ere nonclonal, unbalanced (7 5%), and involved chromosomes 1, 3, 5, 6, 11, 12, 26, and 17 most frequentl y: There rr as also a marked increase of CA in samples at relapse with very similar features (type and distribution) to those detected during treatmen t. There rt as a good correlation between the chromosomal breakpoints in ou r 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 occurr ing at several cancer-associated breakpoints. (C) 2000 Elsevier Science Inc . All rights reserved.