| Autor: |
Felix, Carolyn A., Megonigal, Maureen D., Chervinsky, David S., Leonard, Debra G.B., Tsuchida, Nao, Kakati, Surabhi, Block, Anne Marie W., Fisher, John, Grossi, Mauro, Salhany, Kevin I., Jani-Sait, Sheila N., Aplan, Peter D. |
| Zdroj: |
Blood; June 1998, Vol. 91 Issue: 12 p4451-4456, 6p |
| Abstrakt: |
Segmental jumping translocations are chromosomal abnormalities in treatment-related leukemias characterized by multiple copies of theABLand/or MLLoncogenes dispersed throughout the genome and extrachromosomally. Because gene amplification potential accompanies loss of wild-type p53, we examined the p53 gene in a case of treatment-related acute myeloid leukemia (t-AML) with MLLsegmental jumping translocation. The child was diagnosed with ganglioneuroma and embryonal rhabdomyosarcoma (ERMS) at 2 years of age. Therapy for ERMS included alkylating agents, DNA topoisomerase I and DNA topoisomerase II inhibitors, and local radiation. t-AML was diagnosed at 4 years of age. The complex karyotype of the t-AML showed structural and numerical abnormalities. Fluorescence in situ hybridization analysis showed multiple copies of the MLLgene, consistent with segmental jumping translocation. A genomic region including CD3ε, MLL, and a segment of band 11q24 was unrearranged and amplified by Southern blot analysis. There was no family history of a cancer predisposing syndrome, but single-strand conformation polymorphism (SSCP) analysis detected identical band shifts in the leukemia, ganglioneuroma, ERMS, and normal tissues, consistent with a germline p53 mutation, and there was loss of heterozygosity in the ERMS and the t-AML. Sequencing showed a CGA→TGA nonsense mutation at codon 306 in exon 8. The results of this analysis indicate that loss of wild-type p53 may be associated with genomic instability after DNA-damaging chemotherapy and radiation, manifest as a complex karyotype and gene amplification in some cases of t-AML. |
| Databáze: |
Supplemental Index |
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