Microsatellite instability and p53 mutations in pediatric secondary malignant neoplasms

BACKGROUND. The past decade has witnessed a growing frequency of therapy-re lated secondary tumors. The authors studied nine children with secondary ma lignancies. The primary tumors were bilateral retinoblastoma, neuroblastoma , brain tumor, Wilms' tumor, colon adenocarcinoma, and Hodgkin's disease. T he secondary tumors were osteosarcoma at the site of previous radiotherapy, myelo dysplastic syndrome, acute myelocytic leukemia, glioblastoma, thyroi d carcinoma, and B-cell lymphoma. METHODS. DNA was extracted from the primary and secondary tumors and analyz ed for genetic alterations in the p53 gene and in 7 separate microsatellite s. RESULTS. The authors found p53 mutations in 7 patients, loss of heterozygos ity in 1 patient, and both mutation and loss of heterozygosity in 1 patient . Mutations were demonstrated in the primary tumors only in two patients an d in the secondary tumors only in three patients. Two patients had a mutati on in both the primary and the secondary tumor; in both patients the two mu tations were in different exons. Microsatellite instability (MIN) was ident ified in five to seven loci in the secondary tumors of all patients. CONCLUSIONS. The observed MIN is compatible with the presence of a mutator phenotype that predisposes these children to the development of secondary m alignancies. (C) 1999 American Cancer Society.