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Cytogenetic characterization and gene expression profiling of the trastuzumab-resistant breast cancer cell line JIMT-1.

Rennstam, Karin LU ; Jönsson, Göran B LU ; Tanner, Minna; Bendahl, Pär-Ola LU ; Staaf, Johan LU ; Kapanen, Anita I; Karhu, Ritva; Baldetorp, Bo LU ; Borg, Åke LU and Isola, Jorma (2007) In Cancer Genetics and Cytogenetics1979-01-01+01:002011-01-01+01:00 172(2). p.95-106
Abstract
Resistance to the HER-2 targeting drug trastuzumab can be observed clinically, but the lack of suitable experimental models hampers studies of resistance mechanisms. We characterized a HER-2–positive carcinoma cell line (JIMT-1) derived from a 62-year-old breast cancer patient which was clinically resistant to trastuzumab. Multicolor fluorescence in situ hybridization revealed a complex hyperdiploid karyotype with numerous marker chromosomes and unbalanced translocations. Comparative genomic hybridization (CGH) revealed numerous regions of copy number aberration (CNA). Further analysis by array CGH identified 27 regions of CNA (16 amplified, 11 deleted). Thirty-eight percent of the genes in the amplified regions were overexpressed,... (More)
Resistance to the HER-2 targeting drug trastuzumab can be observed clinically, but the lack of suitable experimental models hampers studies of resistance mechanisms. We characterized a HER-2–positive carcinoma cell line (JIMT-1) derived from a 62-year-old breast cancer patient which was clinically resistant to trastuzumab. Multicolor fluorescence in situ hybridization revealed a complex hyperdiploid karyotype with numerous marker chromosomes and unbalanced translocations. Comparative genomic hybridization (CGH) revealed numerous regions of copy number aberration (CNA). Further analysis by array CGH identified 27 regions of CNA (16 amplified, 11 deleted). Thirty-eight percent of the genes in the amplified regions were overexpressed, compared to only 9% in regions of normal copy number ratios (CNR). Accordingly, 26% of the genes in the deleted regions were underexpressed, compared to 10% in regions of normal CNR. Most amplified and overexpressed genes were located on chromosome 1 as well as on 8q, 12q14.1, 17q11not, vert, similarq21, and 20q13. In 17q11not, vert, similarq21, we identified two separate amplicons, the HER-2 amplicon and a previously unreported amplicon at 17q21.31. Several aberrant genes are implicated in cancer development (e.g., JUN, CDK4, and SLUG protooncogenes, as well as the drug/hormone–metabolizing genes GSTM1 and CYP24). We conclude that cytogenetic and expression profiling of JIMT-1 revealed several new features that need further characterization and may shed light on trastuzumab resistance. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Cancer Genetics and Cytogenetics1979-01-01+01:002011-01-01+01:00
volume
172
issue
2
pages
95 - 106
publisher
Elsevier
external identifiers
  • wos:000243672300001
  • scopus:33845958583
ISSN
0165-4608
DOI
10.1016/j.cancergencyto.2006.09.014
project
CREATE Health
language
English
LU publication?
yes
id
8b74ec57-d901-4540-b03b-429f2e445696 (old id 165024)
date added to LUP
2007-07-04 10:53:00
date last changed
2017-11-05 04:26:08
@article{8b74ec57-d901-4540-b03b-429f2e445696,
  abstract     = {Resistance to the HER-2 targeting drug trastuzumab can be observed clinically, but the lack of suitable experimental models hampers studies of resistance mechanisms. We characterized a HER-2–positive carcinoma cell line (JIMT-1) derived from a 62-year-old breast cancer patient which was clinically resistant to trastuzumab. Multicolor fluorescence in situ hybridization revealed a complex hyperdiploid karyotype with numerous marker chromosomes and unbalanced translocations. Comparative genomic hybridization (CGH) revealed numerous regions of copy number aberration (CNA). Further analysis by array CGH identified 27 regions of CNA (16 amplified, 11 deleted). Thirty-eight percent of the genes in the amplified regions were overexpressed, compared to only 9% in regions of normal copy number ratios (CNR). Accordingly, 26% of the genes in the deleted regions were underexpressed, compared to 10% in regions of normal CNR. Most amplified and overexpressed genes were located on chromosome 1 as well as on 8q, 12q14.1, 17q11not, vert, similarq21, and 20q13. In 17q11not, vert, similarq21, we identified two separate amplicons, the HER-2 amplicon and a previously unreported amplicon at 17q21.31. Several aberrant genes are implicated in cancer development (e.g., JUN, CDK4, and SLUG protooncogenes, as well as the drug/hormone–metabolizing genes GSTM1 and CYP24). We conclude that cytogenetic and expression profiling of JIMT-1 revealed several new features that need further characterization and may shed light on trastuzumab resistance.},
  author       = {Rennstam, Karin and Jönsson, Göran B and Tanner, Minna and Bendahl, Pär-Ola and Staaf, Johan and Kapanen, Anita I and Karhu, Ritva and Baldetorp, Bo and Borg, Åke and Isola, Jorma},
  issn         = {0165-4608},
  language     = {eng},
  number       = {2},
  pages        = {95--106},
  publisher    = {Elsevier},
  series       = {Cancer Genetics and Cytogenetics1979-01-01+01:002011-01-01+01:00},
  title        = {Cytogenetic characterization and gene expression profiling of the trastuzumab-resistant breast cancer cell line JIMT-1.},
  url          = {http://dx.doi.org/10.1016/j.cancergencyto.2006.09.014},
  volume       = {172},
  year         = {2007},
}