PMID- 20300178
OWN - NLM
STAT- MEDLINE
DCOM- 20110111
LR  - 20211020
IS  - 1932-6203 (Electronic)
IS  - 1932-6203 (Linking)
VI  - 5
IP  - 3
DP  - 2010 Mar 11
TI  - A novel translocation breakpoint within the BPTF gene is associated with a 
      pre-malignant phenotype.
PG  - e9657
LID - 10.1371/journal.pone.0009657 [doi]
LID - e9657
AB  - Partial gain of chromosome arm 17q is an abundant aberrancy in various cancer 
      types such as lung and prostate cancer with a prominent occurrence and prognostic 
      significance in neuroblastoma--one of the most common embryonic tumors. The 
      specific genetic element/s in 17q responsible for the cancer-promoting effect of 
      these aberrancies is yet to be defined although many genes located in 17q have 
      been proposed to play a role in malignancy. We report here the characterization 
      of a naturally-occurring, non-reciprocal translocation der(X)t(X;17) in human 
      lung embryonal-derived cells following continuous culturing. This aberrancy was 
      strongly correlated with an increased proliferative capacity and with an acquired 
      ability to form colonies in vitro. The breakpoint region was mapped by 
      fluorescence in situ hybridization (FISH) to the 17q24.3 locus. Further 
      characterization by a custom-made comparative genome hybridization array (CGH) 
      localized the breakpoint within the Bromodomain PHD finger Transcription Factor 
      gene (BPTF), a gene involved in transcriptional regulation and chromatin 
      remodeling. Interestingly, this translocation led to elevation in the mRNA levels 
      of the endogenous BPTF. Knock-down of BPTF restricted proliferation suggesting a 
      role for BPTF in promoting cellular growth. Furthermore, the BPTF chromosomal 
      region was found to be amplified in various human tumors, especially in 
      neuroblastomas and lung cancers in which 55% and 27% of the samples showed gain 
      of 17q24.3, respectively. Additionally, 42% percent of the cancer cell lines 
      comprising the NCI-60 had an abnormal BPTF locus copy number. We suggest that 
      deregulation of BPTF resulting from the translocation may confer the cells with 
      the observed cancer-promoting phenotype and that our cellular model can serve to 
      establish causality between 17q aberrations and carcinogenesis.
FAU - Buganim, Yosef
AU  - Buganim Y
AD  - Department of Molecular Cell Biology, Weizmann Institute of Science, Rehovot, 
      Israel.
FAU - Goldstein, Ido
AU  - Goldstein I
FAU - Lipson, Doron
AU  - Lipson D
FAU - Milyavsky, Michael
AU  - Milyavsky M
FAU - Polak-Charcon, Sylvie
AU  - Polak-Charcon S
FAU - Mardoukh, Corine
AU  - Mardoukh C
FAU - Solomon, Hilla
AU  - Solomon H
FAU - Kalo, Eyal
AU  - Kalo E
FAU - Madar, Shalom
AU  - Madar S
FAU - Brosh, Ran
AU  - Brosh R
FAU - Perelman, Marina
AU  - Perelman M
FAU - Navon, Roy
AU  - Navon R
FAU - Goldfinger, Naomi
AU  - Goldfinger N
FAU - Barshack, Iris
AU  - Barshack I
FAU - Yakhini, Zohar
AU  - Yakhini Z
FAU - Rotter, Varda
AU  - Rotter V
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20100311
PL  - United States
TA  - PLoS One
JT  - PloS one
JID - 101285081
RN  - 0 (Antigens, Nuclear)
RN  - 0 (Carcinogens)
RN  - 0 (Nerve Tissue Proteins)
RN  - 0 (Transcription Factors)
RN  - 0 (fetal Alzheimer antigen)
SB  - IM
MH  - Antigens, Nuclear/*metabolism
MH  - Base Sequence
MH  - Carcinogens
MH  - Cell Proliferation
MH  - Chromosomes, Human, Pair 17
MH  - Comparative Genomic Hybridization/methods
MH  - Humans
MH  - In Situ Hybridization, Fluorescence
MH  - Lung/embryology
MH  - Lung Neoplasms/genetics
MH  - Models, Genetic
MH  - Molecular Sequence Data
MH  - Nerve Tissue Proteins/*metabolism
MH  - Neuroblastoma/metabolism
MH  - Phenotype
MH  - Protein Structure, Tertiary
MH  - Transcription Factors/*metabolism
MH  - *Translocation, Genetic
MH  - Trisomy
PMC - PMC2836376
COIS- Competing Interests: Two of the authors of this manuscript (Dr. Yakhini and Mr. 
      Navon) are employed by Agilent Technologies. Dr. Yakhini designed the probes that 
      were used in the CGH array and analyzed the results. Mr. Navon analyzed the BPTF 
      gene dosage in the NCI-60 cell lines. Agilent Technologies received full payment 
      for Dr. Yakhini's and Mr. Navon's contribution to the manuscript. The authors 
      declare that no patents and/or products in development or marketed products are 
      associated with this manuscript.
EDAT- 2010/03/20 06:00
MHDA- 2011/01/12 06:00
PMCR- 2010/03/11
CRDT- 2010/03/20 06:00
PHST- 2009/12/23 00:00 [received]
PHST- 2010/02/20 00:00 [accepted]
PHST- 2010/03/20 06:00 [entrez]
PHST- 2010/03/20 06:00 [pubmed]
PHST- 2011/01/12 06:00 [medline]
PHST- 2010/03/11 00:00 [pmc-release]
AID - 09-PONE-RA-15153R1 [pii]
AID - 10.1371/journal.pone.0009657 [doi]
PST - epublish
SO  - PLoS One. 2010 Mar 11;5(3):e9657. doi: 10.1371/journal.pone.0009657.