Molecular-cytogenetic analysis of fragmentation of chromosome 17 in the breast cancer cell line EFM-19.
Because a previous study by conventional cytogenetics had revealed a nullisomy 17 in the breast cancer cell line EFM-19, we analysed that cell line by SKY-FISH and by FISH using different probes derived from chromosome 17. A bicolor FISH using a HER2-specific probe and a chromosome 17 centromeric probe showed five HER2 and six centromeric signals all appearing on different chromosomes A further bicolor FISH using a chromosome 17-specific painting probe and a HER2-specific probe revealed that the HER2 signals were always localized within chromosome 17 segments constituting part of structurally altered chromosomes as deduced from their G-banding. Further FISH analyses using single-locus probes of chromosome 17, i.e., for MDS, p53, SMS and RARA, showed that all five chromosome 17 painting segments contained material from the long arm but only two painting segments had additional material from the short arm. A SKY-FISH confirmed the results of the chromosome 17 painting by FISH, except for one structurally altered chromosome showing additional chromosome 17 material detected by the SKY experiment. These results allow us to conclude that, in this cell line, polysomy 17 has preceeded the fragmentation of chromosome 17 leading to amplification of small parts of that chromosome as well as to extended losses. As to a general mechanism, polysomy 17 and a fragility of this, chromosome in breast cancer cells may not only account for part of the cases with HER2 amplification but, at the same time, may further support malignant progression due to the loss of tumor suppressor genes as e.g. p53.
Rogalla
Piere
P
Center for Human Genetics, University of Bremen, Germany.
Helbig
Roger
R
Drieschner
Norbert
N
Flohr
Aljoscha M
AM
Krohn
Maren
M
Bullerdiek
Jörn
J
D001943:Breast Neoplasms / Q000235:genetics*; D002874:Chromosome Mapping; D002886:Chromosomes, Human, Pair 17; D003001:Cloning, Molecular; D053938:DNA Fragmentation; D005260:Female; D005819:Genetic Markers; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D007621:Karyotyping; D008677:Metaphase; D016133:Polymerase Chain Reaction; D014407:Tumor Cells, Cultured
D005819:Genetic Markers