PMID- 9365831 OWN - NLM STAT- MEDLINE DCOM- 19980108 LR - 20191024 IS - 1045-2257 (Print) IS - 1045-2257 (Linking) VI - 20 IP - 3 DP - 1997 Nov TI - Relational mapping of MYCN and DDXI in band 2p24 and analysis of amplicon arrays in double minute chromosomes and homogeneously staining regions by use of free chromatin FISH. PG - 243-52 AB - MYCN amplification has been observed in diverse neuronal tumors including neuroblastoma, retinoblastoma, and small cell carcinoma of the lung, and has been correlated with a poor prognosis in advanced-stage neuroblastomas. Recent studies have shown a co-amplification of DDXI, a DEAD box gene, and MYCN in retinoblastoma and neuroblastoma. DDXI has been mapped to within a megabase of the MYCN gene in band 2p24. In the present study, the relational map of DDXI and MYCN by fluorescence in situ hybridization (FISH) mapping to metaphase cells and extended free chromatin fibers indicated that DDXI is telomeric to MYCN. Dual-color FISH analysis of amplicons within arrays of extended chromatin fibers was performed to examine the physical relationship of MYCN and DDXI within double minute chromosomes (dmins) and homogeneously staining regions (hsrs). No regular reiterated amplicon repeat unit was present in the hsrs, but detailed analysis of the configurations of DDXI and MYCN within each array indicated that multiple rearrangements generated a complex hsr amplicon structure. Similarly, analysis of a cell line bearing dmins showed that a composite amplicon structure involving deletions and/or duplications of MYCN and DDXI is a feature of dmin formation. These data are consistent with a molecular mechanism involving many rearrangements during the evolution of gene amplification, resulting in complex amplicon structures with distinct changes in relative gene copy number and considerable variation in intragenic distances between coamplified genes. FAU - Pandita, A AU - Pandita A AD - Department of Medical Biophysics, University of Toronto, Ontario, Canada. FAU - Godbout, R AU - Godbout R FAU - Zielenska, M AU - Zielenska M FAU - Thorner, P AU - Thorner P FAU - Bayani, J AU - Bayani J FAU - Squire, J A AU - Squire JA LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - United States TA - Genes Chromosomes Cancer JT - Genes, chromosomes & cancer JID - 9007329 RN - 0 (Chromatin) RN - 0 (DNA Probes) RN - 0 (DNA, Neoplasm) RN - EC 2.7.7.- (RNA Nucleotidyltransferases) RN - EC 3.6.1.- (DDX1 protein, human) RN - EC 3.6.4.13 (DEAD-box RNA Helicases) RN - EC 3.6.4.13 (RNA Helicases) SB - IM MH - Blotting, Southern MH - Chromatin MH - *Chromosome Mapping MH - Chromosomes, Human, Pair 2/*genetics MH - DEAD-box RNA Helicases MH - DNA Probes MH - DNA, Neoplasm MH - *Gene Amplification MH - *Gene Rearrangement MH - Genes, myc/*genetics MH - Humans MH - In Situ Hybridization, Fluorescence MH - Multigene Family/genetics MH - *RNA Helicases MH - RNA Nucleotidyltransferases/*genetics MH - Tumor Cells, Cultured EDAT- 1997/11/20 07:04 MHDA- 2000/06/20 09:00 CRDT- 1997/11/20 07:04 PHST- 1997/11/20 07:04 [pubmed] PHST- 2000/06/20 09:00 [medline] PHST- 1997/11/20 07:04 [entrez] AID - 10.1002/(SICI)1098-2264(199711)20:3<243::AID-GCC4>3.0.CO;2-2 [pii] AID - 10.1002/(sici)1098-2264(199711)20:3<243::aid-gcc4>3.0.co;2-2 [doi] PST - ppublish SO - Genes Chromosomes Cancer. 1997 Nov;20(3):243-52. doi: 10.1002/(sici)1098-2264(199711)20:3<243::aid-gcc4>3.0.co;2-2.