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Loss of both CDKN2A and CDKN2B allows for centrosome overduplication in melanoma

Patel, S; Wilkinson, C; Sviderskaya, EV (2020) Loss of both CDKN2A and CDKN2B allows for centrosome overduplication in melanoma. JOURNAL OF INVESTIGATIVE DERMATOLOGY. ISSN 0022-202X https://doi.org/10.1016/j.jid.2020.01.024
SGUL Authors: Sviderskaya, Elena Vladimirovna

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Abstract

Centrosomes duplicate only once in coordination with the DNA replication cycle and have an important role in segregating genetic material. In contrast, the majority of cancer cells have centrosome aberrations including supernumerary centrosomes and this correlates with aneuploidy and genetic instability. The tumour suppressors p16 (CDKN2A) and p15 (CDKN2B) (encoded by the familial melanoma CDKN2 locus) inhibit CDK4/6 activity and have important roles in cellular senescence. p16 is also associated with suppressing centrosomal aberrations in breast cancer; however, the role of p15 in centrosome amplification is unknown. Here we investigated the relationship between p15/p16 expression, centrosome number abnormalities and melanoma progression in cell lines derived from various stages of melanoma progression. We found that normal human melanocyte lines did not exhibit centrosome number abnormalities whereas those from later stages of melanoma did. Additionally, under conditions of S-phase block, p15 and p16 status determined whether centrosome overduplication would occur. Indeed, removal of p15 from p16-negative cell lines derived from various stages of melanoma progression changed cells that previously would not overduplicate their centrosomes into cells that did. While this study used cell lines in vitro, it suggests that, during clinical melanoma progression, sequential loss of p15 and p16 provides conditions for centrosome duplication to become deregulated with consequences for genome instability.

Item Type: Article
Additional Information: © 2020. This manuscript version is made available under the CC-BY-NC-ND 4.0 license http://creativecommons.org/licenses/by-nc-nd/4.0/
Keywords: Dermatology & Venereal Diseases, 1103 Clinical Sciences, 1112 Oncology and Carcinogenesis
SGUL Research Institute / Research Centre: Academic Structure > Molecular and Clinical Sciences Research Institute (MCS)
Journal or Publication Title: JOURNAL OF INVESTIGATIVE DERMATOLOGY
ISSN: 0022-202X
Dates:
DateEvent
15 February 2020Published Online
13 January 2020Accepted
Publisher License: Creative Commons: Attribution-Noncommercial-No Derivative Works 4.0
Projects:
Project IDFunderFunder ID
108429/Z/15/ZWellcome Trusthttp://dx.doi.org/10.13039/100004440
URI: http://openaccess.sgul.ac.uk/id/eprint/111672
Publisher's version: https://doi.org/10.1016/j.jid.2020.01.024

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