Gene copy-number changes and chromosomal instability induced by aneuploidy confer resistance to chemotherapy

Marica Rosaria Ippolito; Valentino Martis; Sara Martin; Andréa E. Tijhuis; Christy Hong; René Wardenaar; Marie Dumont; Johanna Zerbib; Diana C.J. Spierings; Daniele Fachinetti; Uri Ben-David; Floris Foijer; Stefano Santaguida

doi:10.1016/j.devcel.2021.07.006

Gene copy-number changes and chromosomal instability induced by aneuploidy confer resistance to chemotherapy

Marica Rosaria Ippolito, Valentino Martis, Sara Martin, Andréa E. Tijhuis, Christy Hong, René Wardenaar, Marie Dumont, Johanna Zerbib, Diana C.J. Spierings, Daniele Fachinetti, Uri Ben-David, Floris Foijer, Stefano Santaguida

Human Molecular Genetics Biochemistry

Tel Aviv University

Research output: Contribution to journal › Article › peer-review

Abstract

Mitotic errors lead to aneuploidy, a condition of karyotype imbalance, frequently found in cancer cells. Alterations in chromosome copy number induce a wide variety of cellular stresses, including genome instability. Here, we show that cancer cells might exploit aneuploidy-induced genome instability and the resulting gene copy-number changes to survive under conditions of selective pressure, such as chemotherapy. Resistance to chemotherapeutic drugs was dictated by the acquisition of recurrent karyotypes, indicating that gene dosage might play a role in driving chemoresistance. Thus, our study establishes a causal link between aneuploidy-driven changes in gene copy number and chemoresistance and might explain why some chemotherapies fail to succeed.

Original language	English
Pages (from-to)	2440-2454.e6
Journal	Developmental Cell
Volume	56
Issue number	17
DOIs	https://doi.org/10.1016/j.devcel.2021.07.006
State	Published - 13 Sep 2021

Keywords

aneuploidy
cancer
chemotherapy
drug resistance
genome instability

All Science Journal Classification (ASJC) codes

Molecular Biology
General Biochemistry,Genetics and Molecular Biology
Developmental Biology
Cell Biology

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

Access to Document

10.1016/j.devcel.2021.07.006

Cite this

Ippolito, M. R., Martis, V., Martin, S., Tijhuis, A. E., Hong, C., Wardenaar, R., Dumont, M., Zerbib, J., Spierings, D. C. J., Fachinetti, D., Ben-David, U., Foijer, F., & Santaguida, S. (2021). Gene copy-number changes and chromosomal instability induced by aneuploidy confer resistance to chemotherapy. Developmental Cell, 56(17), 2440-2454.e6. https://doi.org/10.1016/j.devcel.2021.07.006

@article{fe070348b146448ca41e4a965d5686b5,

title = "Gene copy-number changes and chromosomal instability induced by aneuploidy confer resistance to chemotherapy",

abstract = "Mitotic errors lead to aneuploidy, a condition of karyotype imbalance, frequently found in cancer cells. Alterations in chromosome copy number induce a wide variety of cellular stresses, including genome instability. Here, we show that cancer cells might exploit aneuploidy-induced genome instability and the resulting gene copy-number changes to survive under conditions of selective pressure, such as chemotherapy. Resistance to chemotherapeutic drugs was dictated by the acquisition of recurrent karyotypes, indicating that gene dosage might play a role in driving chemoresistance. Thus, our study establishes a causal link between aneuploidy-driven changes in gene copy number and chemoresistance and might explain why some chemotherapies fail to succeed.",

keywords = "aneuploidy, cancer, chemotherapy, drug resistance, genome instability",

author = "Ippolito, \{Marica Rosaria\} and Valentino Martis and Sara Martin and Tijhuis, \{Andr{\'e}a E.\} and Christy Hong and Ren{\'e} Wardenaar and Marie Dumont and Johanna Zerbib and Spierings, \{Diana C.J.\} and Daniele Fachinetti and Uri Ben-David and Floris Foijer and Stefano Santaguida",

note = "Publisher Copyright: {\textcopyright} 2021 Elsevier Inc.",

year = "2021",

month = sep,

day = "13",

doi = "10.1016/j.devcel.2021.07.006",

language = "الإنجليزيّة",

volume = "56",

pages = "2440--2454.e6",

journal = "Developmental Cell",

issn = "1534-5807",

publisher = "Cell Press",

number = "17",

}

Ippolito, MR, Martis, V, Martin, S, Tijhuis, AE, Hong, C, Wardenaar, R, Dumont, M, Zerbib, J, Spierings, DCJ, Fachinetti, D, Ben-David, U, Foijer, F & Santaguida, S 2021, 'Gene copy-number changes and chromosomal instability induced by aneuploidy confer resistance to chemotherapy', Developmental Cell, vol. 56, no. 17, pp. 2440-2454.e6. https://doi.org/10.1016/j.devcel.2021.07.006

TY - JOUR

T1 - Gene copy-number changes and chromosomal instability induced by aneuploidy confer resistance to chemotherapy

AU - Ippolito, Marica Rosaria

AU - Martis, Valentino

AU - Martin, Sara

AU - Tijhuis, Andréa E.

AU - Hong, Christy

AU - Wardenaar, René

AU - Dumont, Marie

AU - Zerbib, Johanna

AU - Spierings, Diana C.J.

AU - Fachinetti, Daniele

AU - Ben-David, Uri

AU - Foijer, Floris

AU - Santaguida, Stefano

PY - 2021/9/13

Y1 - 2021/9/13

N2 - Mitotic errors lead to aneuploidy, a condition of karyotype imbalance, frequently found in cancer cells. Alterations in chromosome copy number induce a wide variety of cellular stresses, including genome instability. Here, we show that cancer cells might exploit aneuploidy-induced genome instability and the resulting gene copy-number changes to survive under conditions of selective pressure, such as chemotherapy. Resistance to chemotherapeutic drugs was dictated by the acquisition of recurrent karyotypes, indicating that gene dosage might play a role in driving chemoresistance. Thus, our study establishes a causal link between aneuploidy-driven changes in gene copy number and chemoresistance and might explain why some chemotherapies fail to succeed.

AB - Mitotic errors lead to aneuploidy, a condition of karyotype imbalance, frequently found in cancer cells. Alterations in chromosome copy number induce a wide variety of cellular stresses, including genome instability. Here, we show that cancer cells might exploit aneuploidy-induced genome instability and the resulting gene copy-number changes to survive under conditions of selective pressure, such as chemotherapy. Resistance to chemotherapeutic drugs was dictated by the acquisition of recurrent karyotypes, indicating that gene dosage might play a role in driving chemoresistance. Thus, our study establishes a causal link between aneuploidy-driven changes in gene copy number and chemoresistance and might explain why some chemotherapies fail to succeed.

KW - aneuploidy

KW - cancer

KW - chemotherapy

KW - drug resistance

KW - genome instability

UR - http://www.scopus.com/inward/record.url?scp=85113693491&partnerID=8YFLogxK

U2 - 10.1016/j.devcel.2021.07.006

DO - 10.1016/j.devcel.2021.07.006

M3 - مقالة

C2 - 34352223

SN - 1534-5807

VL - 56

SP - 2440-2454.e6

JO - Developmental Cell

JF - Developmental Cell

IS - 17

ER -

Gene copy-number changes and chromosomal instability induced by aneuploidy confer resistance to chemotherapy

Abstract

Keywords

All Science Journal Classification (ASJC) codes

UN SDGs

Access to Document

Other files and links

Fingerprint

Cite this