Microsatellite instability and p53 mutations in pediatric secondary malignant neoplasms

Ana Gafanovich, Nili Ramu, Svetlana Krichevsky, Jakob Pe'er, Gail Amir, Dina Ben-Yehuda*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

24 Scopus citations

Abstract

BACKGROUND. The past decade has witnessed a growing frequency of therapy-related secondary tumors. The authors studied nine children with secondary malignancies. The primary tumors were bilateral retinoblastoma, neuroblastoma, brain tumor, Wilms' tumor, colon adenocarcinoma, and Hodgkin's disease. The secondary tumors were osteosarcoma at the site of previous radiotherapy, myelodysplastic syndrome, acute myelocytic leukemia, glioblastoma, thyroid carcinoma, and B-cell lymphoma. METHODS. DNA was extracted from the primary and secondary tumors and analyzed for genetic alterations in the p53 gene and in 7 separate microsatellites. RESULTS. The authors found p53 mutations in 7 patients, loss of heterozygosity in 1 patient, and both mutation and loss of heterozygosity in 1 patient. Mutations were demonstrated in the primary tumors only in two patients and in the secondary tumors only in three patients. Two patients had a mutation in both the primary and the secondary tumor; in both patients the two mutations were in different exons. Microsatellite instability (MIN) was identified 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 malignancies.

Original languageEnglish
Pages (from-to)504-510
Number of pages7
JournalCancer
Volume85
Issue number2
DOIs
StatePublished - 1999
Externally publishedYes

Keywords

  • Microsatellite instability
  • Pediatric secondary malignant neoplasms
  • Therapy-related tumors
  • p53 mutations

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