Centromeres in Cancer: Unraveling the Link Between Chromosomal Instability and Tumorigenesis Publisher Pubmed



Karami Fath M¹ ; Nazari A² ; Parsania N³ ; Behboodi P⁴ ; Ketabi SS⁵ ; Razmjouei P² ; Farzam F⁶ ; Shafagh SG⁷ ; Nabi Afjadi M⁶ Show Affiliations
Source: Medical Oncology Published:2024

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. (Figure presented.) © The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature 2024.