Differences and homologies of chromosomal alterations within and between breast cancer cell lines: a clustering analysis
Open accessAbstract
BACKGROUND: The MCF7 (ER+/HER2-), T47D (ER+/HER2-), BT474 (ER+/HER2+) and SKBR3 (ER-/HER2+) breast cancer cell lines are widely used in breast cancer research as paradigms of the luminal and HER2 phenotypes. Although they have been subjected to cytogenetic analysis, their chromosomal abnormalities have not been carefully characterized, and their differential cytogenetic profiles have not yet been established. In addition, techniques such as comparative genomic hybridization (CGH), microarray-based CGH and multiplex ligation-dependent probe amplification (MLPA) have described specific regions of gains, losses and amplifications of these cell lines; however, these techniques cannot detect balanced chromosomal rearrangements (e.g., translocations or inversions) or low frequency mosaicism. RESULTS: A range of 19 to 26 metaphases of the MCF7, T47D, BT474 and SKBR3 cell lines was studied using conventional (G-banding) and molecular cytogenetic techniques (multi-color fluorescence in situ hybridization, M-FISH). We detected previously unreported chromosomal changes and determined the content and frequency of chromosomal markers. MCF7 and T47D (ER+/HER2-) cells showed a less complex chromosomal make up, with more numerical than structural alterations, compared to BT474 and SKBR3 (HER2+) cells, which harbored the highest frequency of numerical and structural aberrations. Karyotype heterogeneity and clonality were determined by comparing all metaphases within and between the four cell lines by hierarchical clustering. The latter analysis identified five main clusters. One of these clusters was characterized by numerical chromosomal abnormalities common to all cell lines, and the other four clusters encompassed cell-specific chromosomal abnormalities. T47D and BT474 cells shared the most chromosomal abnormalities, some of which were shared with SKBR3 cells. MCF7 cells showed a chromosomal pattern that was markedly different from those of the other cell lines. CONCLUSIONS: Our study provides a comprehensive and specific characterization of complex chromosomal aberrations of MCF7, T47D, BT474 and SKBR3 cell lines.The chromosomal pattern of ER+/HER2- cells is less complex than that of ER+/HER2+ and ER-/HER2+ cells. These chromosomal abnormalities could influence the biologic and pharmacologic response of cells. Finally, although gene expression profiling and aCGH studies have classified these four cell lines as luminal, our results suggest that they are heterogeneous at the cytogenetic level.
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Studies with T47D and others suggest similar genotypic and phenotypic heterogeneity.
“For example, studies with T47D - the second most commonly used cell line as an in vitro breast cancer model - as well as others20 suggest similar genotypic and phenotypic heterogeneity212223.”
From Genetic variability in a frozen batch of MCF-7 cells invisible in routine authentication affecting cell function (2016) · cites this paper as [20]
The Results section on T47D reports chromosomal alterations that vary among its metaphases, and the comparison of four cell lines reports distinct chromosomal patterns. These support genotypic heterogeneity, but the paper does not demonstrate phenotypic heterogeneity within T47D or the other cell lines. (LLM, conf=0.84)
Experimental — accuracy not yet measuredMCF-7 are likely not unique in exhibiting such heterogeneity.
“In this respect, MCF-7 are likely not unique. For example, studies with T47D - the second most commonly used cell line as an in vitro breast cancer model - as well as others20 suggest similar genotypic and phenotypic heterogeneity212223.”
From Genetic variability in a frozen batch of MCF-7 cells invisible in routine authentication affecting cell function (2016) · cites this paper as [20]
The Results section on T47D cells (page unavailable) reports variation in chromosomal abnormalities among its 24 metaphases, supporting the point that cytogenetic heterogeneity is not unique to MCF-7. It does not establish phenotypic heterogeneity within T47D, which the citing sentence also attributes to the cited studies. (LLM, conf=0.86)
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- Authors
- Rondón-Lagos, M., Verdun Di Cantogno, L., Marchiò, C., Rangel, N., Payan-Gomez, C., Gugliotta, P., Botta, C., Bussolati, G., Ramírez-Clavijo, S. R., Pasini, B., & Sapino, A.
- Affiliations
- Azienda Ospedaliera Citta' della Salute e della Scienza di Torino (IT)
- University of Turin (IT)
- Universidad del Rosario (CO)
- Corresponding author
- Sapino, Anna
- Venue
- Molecular Cytogenetics
- Published
- 2014-01-23
- Volume
- 7
- Issue
- 1
- Pages
- 8-8
- ISSN
- 1755-8166 (ISSN-L)
- PMC
- PMC3914704
- OpenAlex
- W2162536970
- Cited by
- 43
- References
- 36
- Citations by year
- 2026: 1 · 2025: 2 · 2024: 2 · 2022: 4 · 2021: 5 · 2020: 6 · 2019: 4 · 2018: 5 · 2017: 2 · 2016: 5 · 2015: 5 · 2014: 2
- FWCI
- 3.07
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- cc-by
- Locations
- Molecular Cytogenetics (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- LA Referencia (Red Federada de Repositorios Institucionales de Publicaciones Científicas) (submittedVersion, other-oa)
- RePub (Erasmus University Rotterdam) (submittedVersion, other-oa)
- Institutional Research Information System University of Turin (University of Turin) (submittedVersion, other-oa)
- RePub (Erasmus University Rotterdam) (submittedVersion)
- Greater South Information System
- Funders
- Associazione Italiana per la Ricerca sul Cancro (RF-2010)
- Education, Audiovisual and Culture Executive Agency
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genomic variations and chromosomal abnormalities
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer Genomics and Diagnostics
- Health Sciences › Medicine › Oncology › HER2/EGFR in Cancer Research
- Keywords
- breast cancer cell lines, chromosomal abnormalities, karyotype heterogeneity, MCF-7 cells, T47D cells, BT474 cells, SKBR3, HER2-positive breast cancer, estrogen receptor-positive breast cancer, chromosomal rearrangements, balanced translocation, chromosomal mosaicism, clonality, hierarchical clustering, fluorescence in situ hybridization, metaphase analysis
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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