Unraveling the chromosome 17 patterns of FISH in interphase nuclei: An in-depth analysis of the HER2 amplicon and chromosome 17 centromere by karyotyping, FISH and M-FISH in breast cancer cells

Background: In diagnostic pathology, HER2 status is determined in interphase nuclei by fluorescence in situ hybridization (FISH) with probes for the HER2 gene and for the chromosome 17 centromere (CEP17). The latter probe is used as a surrogate for chromosome 17 copies, however chromosome 17 (Chr17)...

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Autores:
Tipo de recurso:
Fecha de publicación:
2014
Institución:
Universidad del Rosario
Repositorio:
Repositorio EdocUR - U. Rosario
Idioma:
eng
OAI Identifier:
oai:repository.urosario.edu.co:10336/23559
Acceso en línea:
https://doi.org/10.1186/1471-2407-14-922
https://repository.urosario.edu.co/handle/10336/23559
Palabra clave:
Epidermal growth factor receptor 2
Carrier protein
Dna binding protein
Dna topoisomerase (atp hydrolysing)
Dna topoisomerase ii alpha
Membrane protein
Tumor antigen
Amplicon
Article
Breast cancer cell line
Bt474 cell line
Centromere
Chromosome 11
Chromosome 17
Chromosome 8
Chromosome g band
Chromosome rearrangement
Chromosome translocation
Fluorescence in situ hybridization
Gene location
Gene mapping
Human
Human tissue
Interphase
Investigative procedures
Jimt 1 cell line
Karyotyping
Kpl4 cell line
Mcf 7 cell line
Mda mb231 cell line
Mda mb361 cell line
Multicolor fluorescence in situ hybridization
Oncogene
Oncogene neu
Polysome
Signal transduction
Skbr3 cell line
Stard3 gene
T47d cell line
Tnbc case cell line
Top2a gene
Triple negative breast cancer
Zr 75 1 cell line
Carcinoma
Cell nucleus
Centromere
Cytology
Fluorescence in situ hybridization
Gene translocation
Genetics
Interphase
Karyotyping
Metaphase
Procedures
Proto oncogene
Tumor cell line
Carcinoma
Carrier proteins
Cell nucleus
Centromere
Dna-binding proteins
Humans
Interphase
Karyotyping
Membrane proteins
Metaphase
Triple negative breast neoplasms
Breast cancer
Cep17
Chromosomal rearrangements
Chromosome 17
Her2
M-fish
Polysomy
Stard3
Top2a
human
type ii
tumor
neoplasm
genetic
fluorescence
erbb-2
human
pair 17
Stard3 protein
Antigens
Cell line
Chromosomes
Dna topoisomerases
Genes
In situ hybridization
Translocation
Rights
License
Abierto (Texto Completo)
Description
Summary:Background: In diagnostic pathology, HER2 status is determined in interphase nuclei by fluorescence in situ hybridization (FISH) with probes for the HER2 gene and for the chromosome 17 centromere (CEP17). The latter probe is used as a surrogate for chromosome 17 copies, however chromosome 17 (Chr17) is frequently rearranged. The frequency and type of specific structural Chr17 alterations in breast cancer have been studied by using comparative genomic hybridization and spectral karyotyping, but not fully detailed. Actually, balanced chromosome rearrangements (e.g. translocations or inversions) and low frequency mosaicisms are assessable on metaphases using G-banding karyotype and multicolor FISH (M-FISH) only. Methods: We sought to elucidate the CEP17 and HER2 FISH patterns of interphase nuclei by evaluating Chr17 rearrangements in metaphases of 9 breast cancer cell lines and a primary culture from a triple negative breast carcinoma by using G-banding, FISH and M-FISH. Results: Thirty-nine rearranged chromosomes containing a portion of Chr17 were observed. Chromosomes 8 and 11 were the most frequent partners of Chr17 translocations. The lowest frequency of Chr17 abnormalities was observed in the HER2-negative cell lines, while the highest was observed in the HER2-positive SKBR3 cells. The MDA-MB231 triple negative cell line was the sole to show only non-altered copies of Chr17, while the SKBR3, MDA-MB361 and JIMT-1 HER2-positive cells carried no normal Chr17 copies. True polysomy was observed in MDA-MB231 as the only Chr17 alteration. In BT474 cells polysomy was associated to Chr17 structural alterations. By comparing M-FISH and FISH data, in 8 out of 39 rearranged chromosomes only CEP17 signals were detectable, whereas in 14 rearranged chromosomes HER2 and STARD3 genes were present without CEP17 signals. HER2 and STARD3 always co-localized on the same chromosomes and were always co-amplified, whereas TOP2A also mapped to different derivatives and was co-amplified with HER2 and STARD3 on SKBR3 cells only. Conclusion: The high frequency of complex Chr17 abnormalities suggests that the interpretation of FISH results on interphase nuclei using a dual probe assay to assess gene amplification should be performed 'with caution', given that CEP17 signals are not always indicative of normal unaltered or rearranged copies of Chr17. © 2014 Rondón-Lagos et al.