IMR Press / FBL / Volume 10 / Issue 1 / DOI: 10.2741/1567

Frontiers in Bioscience-Landmark (FBL) is published by IMR Press from Volume 26 Issue 5 (2021). Previous articles were published by another publisher on a subscription basis, and they are hosted by IMR Press on imrpress.com as a courtesy and upon agreement with Frontiers in Bioscience.

Open Access Article
Emerging roles of centrosomal amplification and genomic instability in cancer
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1 Department of Pathology, Herbert Irving Comprehensive Cancer Center, Columbia University Medical Center, College of Physicians and Surgeons, New York, New York 10032, USA
2 Department of Urology, Herbert Irving Comprehensive Cancer Center, Columbia University Medical Center, College of Physicians and Surgeons, New York, New York
3 Department of Neurosurgery, Herbert Irving Comprehensive Cancer Center, Columbia University Medical Center, College of Physicians and Surgeons, New York, New York

Academic Editor: Sushanta K. Banerjee

Front. Biosci. (Landmark Ed) 2005, 10(1), 728–742; https://doi.org/10.2741/1567
Published: 1 January 2005
(This article belongs to the Special Issue Growth factors and cancer)
Abstract

The carcinogenic process is multistep in terms of its etiology and multifactor in terms of its evolution. In this context, the temporal accumulation of multiple genetic changes during multistage carcinogenesis that can be mediated at least in part by genomic instability may represent crucial components of tumor cell evolution. Evidence is accumulating indicating a close link between genomic instability and cancer initiation and progression. Neoplastic cells typically possess numerous genomic lesions, which may include sequence alterations (point mutations, small deletions, and insertions) and/or gross structural abnormalities in one or more chromosomes (large-scale deletions, rearrangements, gene amplifications). Furthermore karyotypic alterations, including whole chromosome loss or gain, ploidy changes (aneuploidy and polyploidy) and a variety of chromosome aberrations are common in tumor cells. Genomic instability also involves mitotic defects associated with centrosome abnormalities. However, the question of whether abnormal centrosomes cause genomic instability or develop secondary to other changes has not been conclusively resolved. In this review, the recent studies investigating genomic instability and aneuploidy in human cancer, centrosome amplification and the role of centrosomal duplication in chromosomal mis-segregetion, and genes implicated in regulating chromosome segregation, centrosomal amplification and progression in cancer cells are discussed.

Keywords
Genomic instability
chromosomal instability
aneuploidy
centrosome
centrosomal amplification
cell cycle proteins
Review
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