Role of chromosomal instability and clonal heterogeneity in the therapy response of breast cancer cell lines

Natalia Vargas-Rondón, Erika Pérez-Mora, Victoria E. Villegas, Milena Rondón-Lagos

Research output: Contribution to journalResearch Articlepeer-review

10 Scopus citations


Objective: Chromosomal instability (CIN) is a hallmark of cancer characterized by cell-to-cell variability in the number or structure of chromosomes, frequently observed in cancer cell populations and is associated with poor prognosis, metastasis, and therapeutic resistance. Breast cancer (BC) is characterized by unstable karyotypes and recent reports have indicated that CIN may influence the response of BC to chemotherapy regimens. However, paradoxical associations between extreme CIN and improved outcome have been observed. Methods: This study aimed to 1) evaluate CIN levels and clonal heterogeneity (CH) in MCF7, ZR-751, MDA-MB468, BT474, and KPL4 BC cells treated with low doses of tamoxifen (TAM), docetaxel (DOC), doxorubicin (DOX), Herceptin (HT), and combined treatments (TAM/DOC, TAM/DOX, TAM/HT, HT/DOC, and HT/DOX) by using fluorescence in situ hybridization (FISH), and 2) examine the association with response to treatments by comparing FISH results with cell proliferation. Results: Intermediate CIN was linked to drug sensitivity according to three characteristics: estrogen receptor α (ERα) and HER2 status, pre-existing CIN level in cancer cells, and the CIN induced by the treatments. ERα+/HER2- cells with intermediate CIN were sensitive to treatment with taxanes (DOC) and anthracyclines (DOX), while ERα-/HER2-, ERα+/HER2+, and ERα-/HER2+ cells with intermediate CIN were resistant to these treatments. Conclusions: A greater understanding of CIN and CH in BC could assist in the optimization of existing therapeutic regimens and/or in supporting new strategies to improve cancer outcomes.

Translated title of the contributionRol de la inestabilidad cromosómica y la heterogeneidad clonal en la respuesta a terapia de líneas celulares de cáncer de mama
Original languageEnglish (US)
Pages (from-to)970-985
Number of pages16
JournalCancer Biology and Medicine
Issue number4
StatePublished - Dec 15 2020

All Science Journal Classification (ASJC) codes

  • Oncology
  • Cancer Research


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