Microsatellite instability and p53 mutations in pediatric secondary malignant neoplasms

Autor: Nili Ramu, Gail Amir, Ana Gafanovich, Jakob Pe'er, Svetlana Krichevsky, Dina Ben-Yehuda
Rok vydání: 1999
Předmět:
Zdroj: Cancer. 85:504-510
ISSN: 1097-0142
0008-543X
DOI: 10.1002/(sici)1097-0142(19990115)85:2<504::aid-cncr32>3.0.co;2-c
Popis: 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. Cancer 1999;85:504–10. © 1999 American Cancer Society.
Databáze: OpenAIRE
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