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01-11-2024 | Fluorescence in Situ Hybridization | Review Article

Centromeres in cancer: Unraveling the link between chromosomal instability and tumorigenesis

Authors: Mohsen Karami Fath, Ahmad Nazari, Noushin Parsania, Paria Behboodi, Seyedeh Sara Ketabi, Pegah Razmjouei, Farnoosh Farzam, Seyyed-Ghavam Shafagh, Mohsen Nabi Afjadi

Published in: Medical Oncology | Issue 11/2024

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Abstract

Centromeres are critical structures involved in chromosome segregation, maintaining genomic stability, and facilitating the accurate transmission of genetic information. They are key in coordinating the assembly and help keep the correct structure, location, and function of the kinetochore, a proteinaceous structure vital for ensuring proper chromosome segregation during cell division. Abnormalities in centromere structure can lead to aneuploidy or chromosomal instability, which have been implicated in various diseases, including cancer. Accordingly, abnormalities in centromeres, such as structural rearrangements and dysregulation of centromere-associated proteins, disrupt gene function, leading to uncontrolled cell growth and tumor progression. For instance, altered expression of CENP-A, CENP-E, and others such as BUB1, BUBR1, MAD1, and INCENP, have been shown to ascribe to centromere over-amplification, chromosome missegregation, aneuploidy, and chromosomal instability; this, in turn, can culminate in tumor progression. These centromere abnormalities also promoted tumor heterogeneity by generating genetically diverse cell populations within tumors. Advanced techniques like fluorescence in situ hybridization (FISH) and chromosomal microarray analysis are crucial for detecting centromere abnormalities, enabling accurate cancer classification and tailored treatment strategies. Researchers are exploring strategies to disrupt centromere-associated proteins for targeted cancer therapies. Thus, this review explores centromere abnormalities in cancer, their molecular mechanisms, diagnostic implications, and therapeutic targeting. It aims to advance our understanding of centromeres’ role in cancer and develop advanced diagnostic tools and targeted therapies for improved cancer management and treatment.

Graphical abstract

Numerical and structural chromosomal instability are genetic alterations that can lead to cancer development. Numerical instability results from abnormal chromosome numbers, while structural instability involves alterations in chromosome structure, disrupting gene function and forming fusion genes. These alterations can lead to genomic instability, promoting uncontrolled cell growth and cancers.
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Metadata
Title
Centromeres in cancer: Unraveling the link between chromosomal instability and tumorigenesis
Authors
Mohsen Karami Fath
Ahmad Nazari
Noushin Parsania
Paria Behboodi
Seyedeh Sara Ketabi
Pegah Razmjouei
Farnoosh Farzam
Seyyed-Ghavam Shafagh
Mohsen Nabi Afjadi
Publication date
01-11-2024
Publisher
Springer US
Published in
Medical Oncology / Issue 11/2024
Print ISSN: 1357-0560
Electronic ISSN: 1559-131X
DOI
https://doi.org/10.1007/s12032-024-02524-0

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