Document Detail

Expulsion of amplified MYCN from homogenously staining chromosomal regions in neuroblastoma cell lines after cultivation with cisplatin, doxorubicin, hydroxyurea, and vincristine.
MedLine Citation:
PMID:  19963143     Owner:  NLM     Status:  MEDLINE    
Amplified MYCN, common in neuroblastomas, can be detected as double minutes (dmin) or homogenously staining chromosomal regions (hsr). Expulsion of amplified MYCN has only been described in dmin. We used hydroxyurea (HU), which accelerates the expulsion of amplified genes and cytostatics (used in neuroblastoma therapy), to describe MYCN amplification changes after chemotherapy. We used IMR-32, SK-N-AS, UKF-NB-2, UKF-NB-3, UKF-NB-4, and derived sublines resistant to doxorubicin, cisplatin, and vincristine. The loss of amplified MYCN copies was investigated using comparative genomic hybridization and by fluorescent in situ hybridization. We found expulsion of amplified MYCN from hsr in UKF-NB-4 and IMR-32 cell lines, and determined the exact number of amplified MYCN copies. After the first cultivation with HU, some amplified MYCN was lost. UKF-NB-4 lost 20 copies on average, and IMR-32 lost 15 copies (P<0.001). After the second cultivation, cells without MYCN amplification were found. In comparison to sensitive cell lines, drug-resistant cell lines lost 17 copies on average. Our data show that expulsion of amplified MYCN genes is also possible from hsr and may be induced, not only by HU, but by other cytostatics as well.
Pavel Prochazka; Jan Hrabeta; Ales V??cha; Tomas Eckschlager
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Cancer genetics and cytogenetics     Volume:  196     ISSN:  1873-4456     ISO Abbreviation:  Cancer Genet. Cytogenet.     Publication Date:  2010 Jan 
Date Detail:
Created Date:  2009-12-07     Completed Date:  2009-12-17     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  7909240     Medline TA:  Cancer Genet Cytogenet     Country:  United States    
Other Details:
Languages:  eng     Pagination:  96-104     Citation Subset:  IM    
Department of Pediatric Hematology and Oncology, Charles University in Prague - 2nd Medical School, V Uvalu 84, Prague 15006, Czech Republic.
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MeSH Terms
Antineoplastic Combined Chemotherapy Protocols / administration & dosage*
Cell Cycle
Cell Line, Tumor
Cisplatin / administration & dosage
Doxorubicin / administration & dosage
Genes, myc*
Hydroxyurea / administration & dosage
In Situ Hybridization, Fluorescence
Neuroblastoma / genetics*,  pathology
Vincristine / administration & dosage
Reg. No./Substance:
127-07-1/Hydroxyurea; 15663-27-1/Cisplatin; 23214-92-8/Doxorubicin; 57-22-7/Vincristine

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