PMID- 18656688
OWN - NLM
STAT- MEDLINE
DCOM- 20080815
LR  - 20080728
IS  - 1873-4456 (Electronic)
IS  - 0165-4608 (Linking)
VI  - 185
IP  - 1
DP  - 2008 Aug
TI  - The complicated copy number alterations in chromosome 7 of a lung cancer cell 
      line is explained by a model based on repeated breakage-fusion-bridge cycles.
PG  - 11-9
LID - 10.1016/j.cancergencyto.2008.04.005 [doi]
AB  - The drug-resistant lung cancer cell line PTX250, which has been previously 
      established by exposure to an anti-cancer drug paclitaxel, has an increased copy 
      number in the MDR1/ABCB1 locus region. In addition, the flanking regions also 
      exhibit aberrant copy numbers, making the copy number profile of chromosome 7 
      complicated. In this study, we tested whether the breakage-fusion-bridge (BFB) 
      cycle model can explain such copy number alterations. An analysis using 
      fluorescence in situ hybridization (FISH) with a painting probe demonstrated that 
      the aberrant chromosome, designated chromosome 7(amp), was derived from an intact 
      chromosome 7. Using high-density comparative genomic hybridization arrays, we 
      examined the copy number profile in detail and divided chromosome 7(amp) into 
      seven segments. Based on copy numbers of each segment, which were determined 
      using interphase- and metaphase-FISH analysis, we constructed a formation model 
      for the complicated copy number alteration. Six-time BFB cycles and the 
      cycle-termination by healing of broken ends were presupposed in the model. 
      Locations and orientations of the segments observed in chromosome 7(amp) agreed 
      well with those predicted from the model. Telomere addition was also 
      cytogenetically confirmed. In all, it could be concluded that the complicated 
      copy number alteration found in chromosome 7(amp) is generated from the intact 
      chromosome 7 by the repeated BFB cycles.
FAU - Kitada, Kunio
AU  - Kitada K
AD  - Kamakura Research Laboratories, Chugai Pharmaceutical Co. Ltd., 200-Kajiwara, 
      Kamakura, Kanagawa 247-8530, Japan. kitadakno@chugai-pharm.co.jp
FAU - Yamasaki, Tomoaki
AU  - Yamasaki T
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Cancer Genet Cytogenet
JT  - Cancer genetics and cytogenetics
JID - 7909240
SB  - IM
MH  - Carcinoma, Non-Small-Cell Lung/genetics/pathology
MH  - *Cell Line, Tumor
MH  - *Chromosome Aberrations
MH  - Chromosome Painting
MH  - *Chromosomes, Human, Pair 7
MH  - Gene Amplification
MH  - *Gene Dosage
MH  - Humans
MH  - In Situ Hybridization, Fluorescence
MH  - Lung Neoplasms/genetics/pathology
MH  - *Models, Genetic
MH  - Oligonucleotide Array Sequence Analysis
EDAT- 2008/07/29 09:00
MHDA- 2008/08/16 09:00
CRDT- 2008/07/29 09:00
PHST- 2008/02/08 00:00 [received]
PHST- 2008/03/31 00:00 [revised]
PHST- 2008/04/07 00:00 [accepted]
PHST- 2008/07/29 09:00 [pubmed]
PHST- 2008/08/16 09:00 [medline]
PHST- 2008/07/29 09:00 [entrez]
AID - S0165-4608(08)00234-3 [pii]
AID - 10.1016/j.cancergencyto.2008.04.005 [doi]
PST - ppublish
SO  - Cancer Genet Cytogenet. 2008 Aug;185(1):11-9. doi: 
      10.1016/j.cancergencyto.2008.04.005.