PMID- 11221853
OWN - NLM
STAT- MEDLINE
DCOM- 20010315
LR  - 20061115
IS  - 0008-5472 (Print)
IS  - 0008-5472 (Linking)
VI  - 61
IP  - 3
DP  - 2001 Feb 1
TI  - Chromosomal rearrangements and oncogene amplification precede aneuploidization in 
      the genetic evolution of breast cancer.
PG  - 1214-9
AB  - Breast carcinoma is thought to arise because of multiple successive changes in 
      the genome of the normal epithelial cells. However, little is known of the order 
      of appearance of different types of genetic aberrations We studied the ERBB2 
      (Her-2/neu) and CCND1 (cyclin D1) oncogene amplification in flow cytometrically 
      sorted diploid and nondiploid tumor cell populations by fluorescence in situ 
      hybridization (FISH). The purity of the cell sorting was confirmed by static DNA 
      image cytometry. Spectral karyotyping was used to define differences in a 
      genome-wide manner between two distinctly different aneuploid cell clones found 
      in each of two breast cancer cell lines. FISH indicated the presence of gene 
      amplification both in diploid and nondiploid cell clones in 17 of the 21 
      amplification-containing tumors analyzed. The oncogene copy numbers remained 
      unchanged throughout aneuploidization in 11 of 17 tumors. The remaining six 
      tumors showed an increase in oncogene copy number as well as the number of 
      chromosome 11 or 17 centromeres (the original location of CCNDI and ERBB2, 
      respectively). Breast carcinoma cell lines MDA-157 and MDA-436 showed a 
      significant number of chromosomal rearrangements in the near-diploid clones, 
      which were present in duplicate in the corresponding aneuploid (polyploid) 
      clones. These results indicate that ploidy shift, ie., aneuploidization, in 
      breast cancer is a late genetic event which is preceded by both oncogene 
      amplifications as well as many chromosomal rearrangements.
FAU - Rennstam, K
AU  - Rennstam K
AD  - Department of Oncology, Jubileum Institute, University Hospital, Lund, Sweden. 
      Karin.Rennstam@onk.lu.se
FAU - Baldetorp, B
AU  - Baldetorp B
FAU - Kytola, S
AU  - Kytola S
FAU - Tanner, M
AU  - Tanner M
FAU - Isola, J
AU  - Isola J
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Cancer Res
JT  - Cancer research
JID - 2984705R
RN  - 136601-57-5 (Cyclin D1)
SB  - IM
MH  - *Aneuploidy
MH  - Breast Neoplasms/*genetics
MH  - Chromosome Aberrations
MH  - Cyclin D1/genetics
MH  - Diploidy
MH  - Flow Cytometry
MH  - *Gene Amplification
MH  - Gene Dosage
MH  - *Gene Rearrangement
MH  - Genes, erbB-2
MH  - Humans
MH  - In Situ Hybridization, Fluorescence
MH  - Karyotyping
EDAT- 2001/02/28 10:00
MHDA- 2001/03/17 10:01
CRDT- 2001/02/28 10:00
PHST- 2001/02/28 10:00 [pubmed]
PHST- 2001/03/17 10:01 [medline]
PHST- 2001/02/28 10:00 [entrez]
PST - ppublish
SO  - Cancer Res. 2001 Feb 1;61(3):1214-9.