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  • Oncogenomics
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High-resolution array CGH analysis of salivary gland tumors reveals fusion and amplification of the FGFR1 and PLAG1 genes in ring chromosomes

Oncogene volume 27, pages 3072–3080 (2008)Cite this article

Abstract

We have previously identified a subgroup of pleomorphic salivary gland adenomas with ring chromosomes of uncertain derivation. Here, we have used spectral karyotyping (SKY), fluorescence in situ hybridization (FISH) and high-resolution oligonucleotide array-CGH to determine the origin and content of these rings and to identify genes disrupted as a result of ring formation. Of 16 tumors with rings, 11 were derived from chromosome 8, 3 from chromosome 5 and 1 each from chromosomes 1, 6 and 9. Array-CGH revealed that 10/11 r(8) consisted of amplification of a 19 Mb pericentromeric segment with recurrent breakpoints in FGFR1 in 8p12 and in PLAG1 in 8q12.1. Molecular analyses revealed that ring formation consistently generated novel FGFR1–PLAG1 gene fusions in which the 5′-part of FGFR1 is linked to the coding sequence of PLAG1. An alternative mechanism of PLAG1 activation was found in tumors with copy number gain of an intact PLAG1 gene. Rings derived from chromosomes 1, 5, 6 or 9 did not result in gene fusions, but rather resulted in losses indicative of the involvement of putative tumor suppressor genes on 8p, 5p, 5q and/or 6q. Our findings also reveal a novel mechanism by which FGFR1 contributes to oncogenesis and further illustrate the versatility of the FGFR1 and PLAG1 genes in tumorigenesis.

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Acknowledgements

We thank Ulric Pedersen for expert help with the illustrations. This work was supported by grants from the Swedish Cancer Society, the IngaBritt and Arne Lundberg Research Foundation, the Assar Gabrielsson Research Foundation for Clinical Cancer Research and the Sahlgrenska University Hospital Foundations.

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Authors and Affiliations

  1. Department of Pathology, Lundberg Laboratory for Cancer Research, Sahlgrenska University Hospital, Göteborg University, Göteborg, Sweden

    F Persson, M Winnes, Y Andrén, B Wedell, J Asp, F Enlund & G Stenman

  2. Department of Pathology, Central Hospital, Skövde, Sweden

    R Dahlenfors & J Mark

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  1. F Persson
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  2. M Winnes
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  3. Y Andrén
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Correspondence to G Stenman.

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Persson, F., Winnes, M., Andrén, Y. et al. High-resolution array CGH analysis of salivary gland tumors reveals fusion and amplification of the FGFR1 and PLAG1 genes in ring chromosomes. Oncogene 27, 3072–3080 (2008). https://doi.org/10.1038/sj.onc.1210961

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