Neoplasma Vol.52, p.415-419, 2005
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Title: Characterization of drug-resistant neuroblastoma cell lines by comparative genomic hybridization
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Author: J., BEDRNICEK
; A., VICHA
; M., JAROSOVA
; M., HOLZEROVA
; J., CINATL, JR.
; M., MICHAELIS
; J., CINATL
; T., ECKSCHLAGER
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Abstract: Three parental neuroblastoma cell lines and nine derived lines resistant to Vincristin, Doxorubicin and Cisplatin, respectively,
using CGH were studied. CGH profiles of all three parental cell lines were obtained usingDNAfrom a healthy volunteer
as reference DNA. Labeled DNAfrom each of the drug resistant daughter cell lines and labeled DNAfrom their parental
sensitive cell lines were hybridized to obtain a comparison of gains and losses that accompanied the development of resistance
for that particular drug. All three parental cell lines were characterized by typical findings for high risk neuroblastoma:
N-myc amplification, gain of 17q, and loss of 1p36.2-36.3. Acquired drug resistance in the neuroblastoma cell lines appeared
to be accompanied by a large array of DNA sequence copy number changes. The regions frequently affected in
chemoresistant cell lines included gains of 13q14.1-32, and 7q11.2-31.3, 4q. Amplifications were seen at 7q 21.1 consistent
with MDR1 amplification in UKF-NB-2 VCR, UKF-NB-3 DOXO, UKF-NB-4 VCR, and UKF-NB-4 DOXO, but not in
any Cisplatin resistant line. All Cisplatin and Doxorubicin and two Vincristin resistant line (UKF-NB-2 VCR and
UKF-NB-4 VCR) had a deletion of part of 19q or the whole 19 chromosome. All lines resistant to Vincristin or Doxorubicin
and two Cisplatin resistant lines (UKF-NB-2 CDDP and UKF-NB-4 CDDP) had a deletion of at least part of 17q,
UKF-NB-4 DOXO had deletion of the whole chromosome 17. The loss of 17q may cause chemoresistance by deletion of
topoisomerase II? gene. Deletion of 19q in all but one chemoresistant lines may influence of cytochromes P450 genes
which are located on 19q13.2. Also gains of 15q22, which were detected in UKF-NB-4 VCR, UKF-NB-2 DOXO and
UKF-NB-4 DOXO, may affect other cytochromes P450 genes.
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Keywords: neuroblastoma, comparative genomic hybridization, chemoresistance
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Year: 2005, Volume: 52, Issue: |
Page From: 415, Page To: 419 |
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