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Association of CDK4 and CCND1 mRNA overexpression in laryngeal squamous cell carcinomas occurs without CDK4 amplification

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Abstract

CDK4 is involved in the control of G1–S phase transition as a part of the CCND1/CDK4 complexes. CCND1 and CDK4 gene alterations have been implicated in the development of different tumors. CCND1 has been associated with progression in laryngeal carcinomas. CDK4 protein overexpression was described associated to CCND1 overexpression in these tumors. However, the mechanisms implicated were not known. We analyzed CDK4 gene alterations and mRNA expression in a series of carcinomas of the larynx, and the results were compared to CCND1 expression and clinicopathological characteristics of the patients. CDK4 mRNA was overexpressed in 42 out of 60 tumors (70%) associated with CCND1 mRNA overexpression because 15 out of 16 cases with high CCND1 levels showed simultaneous increased levels of CDK4 mRNA (p = 0.023) and 12 (87%) of the tumors overexpressing both genes were in stage 4. No CDK4 gene amplifications, rearrangements, or mutations were detected in any of the tumors, including 24 overexpressed cases. These findings confirm that CDK4 overexpression is a frequent phenomenon in laryngeal carcinomas, which occurs at the transcriptional level but is related neither to gene amplification nor to gene mutation, and suggest that cooperation with CCND1 may be involved in the progression of laryngeal tumors.

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Acknowledgements

This study was supported in part by grants from Fondo de Investigación Sanitaria (FIS), Instituto de Salud Carlos III, ref. 030407, Red Temática del Cáncer, Instituto de Salud Carlos III, n°C03/10, and Junta de Comarques de Barcelona de la Asociación Española Contra el Cáncer.

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Authors and Affiliations

  1. Anatomia Patologica, Hospital Clínic, Institut d’Investigacions Biomediques “August Pi i Sunyer” (IDIBAPS), Villarroel 170, Barcelona, Spain

    Alfons Nadal, Pedro L. Fernández, Elías Campo & Antonio Cardesa

  2. Departament de Biologia Cel·lular i Anatomia Patológica, Universitat de Barcelona, Casanovas 143, 08036, Barcelona, Spain

    Alfons Nadal, Pedro L. Fernández, Elías Campo & Antonio Cardesa

  3. Genomics Unit, Institut d’Investigacions Biomediques “August Pi i Sunyer”(IDIBAPS), Universitat de Barcelona, Villarroel 170, 08036, Barcelona, Spain

    Pedro Jares & Magda Pinyol

  4. Fundació Clínic per a la Recerca Biomédica, Villarroel 170, 08036, Barcelona, Spain

    Laura Conde

  5. Hospital de Ntra. Sra. de Meritxell, Avda. Fiter i Rossell, 1-13, Escaldes-Engordany, Principat d’Andorra

    Coia Romeu

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  1. Alfons Nadal
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  2. Pedro Jares
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  3. Magda Pinyol
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  4. Laura Conde
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  6. Pedro L. Fernández
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  7. Elías Campo
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  8. Antonio Cardesa
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Correspondence to Alfons Nadal.

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Nadal, A., Jares, P., Pinyol, M. et al. Association of CDK4 and CCND1 mRNA overexpression in laryngeal squamous cell carcinomas occurs without CDK4 amplification. Virchows Arch 450, 161–167 (2007). https://doi.org/10.1007/s00428-006-0314-2

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  • DOI: https://doi.org/10.1007/s00428-006-0314-2

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