Abstract
We reinvestigated rearrangements occurring in region q13 of chromosome 11 aiming to: (i) describe heterogeneity of the observed structural alterations, (ii) estimate amplicon size and (iii) identify of oncogenes involved in laryngeal cancer progression as potential targets for therapy. The study included 17 cell lines derived from laryngeal cancers and 34 specimens from primary laryngeal tumors. The region 11q13 was analyzed by fluorescence in situ hybridization (FISH), array comparative genomic hybridization (aCGH) and gene expression microarray. Next, quantitative real time PCR was used for chosen genes to confirm results from aCGH and gene expression microarray. The observed pattern of aberrations allows to distinguish three ways, in which gain and amplification involving 11q13 region may occur: formation of a homogeneously staining region; breakpoints in/near 11q13, which lead to the three to sevenfold increase of the copy number of 11q13 region; the presence of additional copies of the whole chromosome 11. The minimal altered region of gain and/or amplification was limited to ~1.8 Mb (chr.11:69,395,184–71,209,568) and comprised mostly 11q13.3 band which contain 12 genes. Five, out of these genes (CCND1, ORAOV1, FADD, PPFIA1, CTTN) had higher expression levels in comparison to healthy controls. Apart from CCND1 gene, which has an established role in pathogenesis of head and neck cancers, CTTN, ORAOV1 and FADD genes appear to be oncogene-candidates in laryngeal cancers, while a function of PPFIA1 requires further studies.
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Abbreviations
- BAC:
-
Bacterial artificial chromosome
- CGH array:
-
Comparative genome hybridization
- HNSCC:
-
Head neck squamous cell carcinoma
- HPV:
-
Human papilloma virus
- LSCC:
-
Laryngeal squamous cell carcinoma
- MAR:
-
Minimal altered region
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Acknowledgments
This work was funded by the Polish Ministry of Science and Higher Education Grants, numbers N 403 03 232/1989 and N 401 192 32/4031. We thank Prof. Reiner Siebert (Institute of Human Genetics, University Hospital Schleswig-Holstein Campus Kiel, Christian—Albrechts University 24105 Kiel, Germany) for possibility to perform microarray CGH experiments.
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The authors declare that they have no conflict of interest.
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We declare that all experiments were performed in accordance with the current law of Poland.
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Jarmuz-Szymczak, M., Pelinska, K., Kostrzewska-Poczekaj, M. et al. Heterogeneity of 11q13 region rearrangements in laryngeal squamous cell carcinoma analyzed by microarray platforms and fluorescence in situ hybridization. Mol Biol Rep 40, 4161–4171 (2013). https://doi.org/10.1007/s11033-013-2496-4
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DOI: https://doi.org/10.1007/s11033-013-2496-4