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Genetic Changes in Sporadic Keratocystic Odontogenic Tumors (Odontogenic Keratocysts)

K. Heikinheimo^1,2,,*, K.J. Jee^3,, P.R. Morgan⁴, B. Nagy⁵, S. Knuutila³ and I. Leivo³

¹ Department of Oral and Maxillofacial Surgery, Institute of Dentistry, University of Turku, Lemminkäisenkatu 2, FIN-20520 Turku, Finland;
² Department of Oral Diseases, Turku University Hospital, Lemminkäisenkatu 2, FIN-20500 Turku, Finland;
³ Haartman Institute, Department of Pathology, FIN-00014 University of Helsinki, Finland;
⁴ Department of Oral Pathology, GKT Dental Institute, King’s College London, United Kingdom; and
⁵ Genetic Laboratory, 1st Department of Obstetrics and Gynecology, Semmelweis University, Budapest, Hungary

View larger version (27K): [in this window] [in a new window]   Figure 1. Distribution of gene expression in sporadic KCOT determined by cDNA array and visualized in Treeview. Cases 1–10 are shown in columns and genes in rows. Data of the 20 most highly over- and under-expressed genes are shown. Difference in gene expression from controls (normal human tooth germ) is displayed in descending order (over-expressed genes), and in ascending order (under-expressed genes). Over-expressed genes are shown in red, under-expressed genes in green. The most over-expressed gene is KRT6B, and the most under-expressed is CSPG2.

View larger version (77K): [in this window] [in a new window]   Figure 2. Relative expression of genes in 12q as observed by quantitative real-time reverse-transcription/polymerase chain-reaction (QRT-PCR), and immunolocalization of protein products by immunohistochemistry. (A) X-axis indicates cases (1–4, 6, 11, and 12) analyzed. Normalized ratios (obtained with the housekeeping gene PL2A) of gene expression for each gene are plotted on the Y-axis. The graph shows over-expression of KRT6, DDIT3, ERBB3, and GLI1 in all seven cases (except for ERBB3 in case 6, and GLI1 in case 3). ITGA7 was under-expressed in all seven cases, except case 4. (B) Positive immunoreactivity with KRT6B and ERBB3 antibodies was seen in suprabasal cell layers of tumor epithelium. When stained, HBEGF antibodies showed positive reactivity in basal epithelial cells and a few suprabasal epithelial cells. GLI1 antibodies showed positive reactivity in all epithelial cell layers. Scale bars, A–D, 50 µm.

View larger version (24K): [in this window] [in a new window]   Figure 3. Array-comparative genomic hybridization profile of gene amplifications in pooled DNA from cases 8, 11, and 12. Gene amplifications in 12q13.2 reveal amplicon (0.7 Mbp) of 15 consecutive amplified genes. CI = chromosomal idiogram, P = composite of oligo probe dots. Color indicates ratio of gene copy number to normal reference DNA, AG = region of gene amplification indicated by blue bar, M = magnification of amplified genomic region. Some known genes are plotted in the amplified region. N = genomic nucleotide scale bar.

Journal of Dental Research, Vol. 86, No. 6, 544-549 (2007)
DOI: 10.1177/154405910708600611


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