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High-resolution mapping identifies a commonly amplified 11q13.3 region containing multiple genes flanked by segmental duplications

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Abstract

DNA amplification of the 11q13 region is observed frequently in many carcinomas. Within the amplified region several candidate oncogenes have been mapped, including cyclin D1, TAOS1 and cortactin. Yet, it is unknown which gene(s) is/are responsible for the selective pressure enabling amplicon formation. This is probably due to the use of low-resolution detection methods. Furthermore, the size and structure of the amplified 11q13 region is complex and consists of multiple amplicon cores that differ between different tumor types. We set out to test whether the borders of the 11q13 amplicon are restricted to regions that enable DNA breakage and subsequent amplification. A high-resolution array of the 11q13 region was generated to study the structure of the 11q13 amplicon and analyzed 29 laryngeal and pharyngeal carcinomas and nine cell lines with 11q13 amplification. We found that boundaries of the commonly amplified region were restricted to four segments. Three boundaries coincided with a syntenic breakpoint. Such regions have been suggested to be putatively fragile. Sequence comparisons revealed that the amplicon was flanked by two large low copy repeats known as segmental duplications. These segmental duplications might be responsible for the typical structure and size of the 11q13 amplicon. We hypothesize that the selection for genes through amplification of the 11q13.3 region is determined by the ability to form DNA breaks within specific regions and, consequently, results in large amplicons containing multiple genes.

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Acknowledgment

We would like to thank Trijnie Dijkhuizen, Pieter van der Vlies and Itty Oostendorp for technical assistance. We are grateful to Jane Briggs for reading the manuscript. This work is financially supported by the foundations of “Nijbakker-Morra”, “De Drie Lichten”, “Maurits en Anna de Kock” and the Groningen University Institute for Drug Exploration (GUIDE) in the Netherlands.

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  1. Department of Pathology, University Medical Center Groningen, University of Groningen, PO Box 30001, 9700 RB, Groningen, The Netherlands

    Johan H. Gibcus, Lorian Menkema, Mirjam Mastik, Philip M. Kluin, Jacqueline E. van der Wal & Ed Schuuring

  2. Department of Clinical Genetics, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands

    Klaas Kok

  3. Department of Otolaryngology, Hospital Universitario Central de Asturias, Oviedo, Spain

    Mario A. Hermsen

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  1. Johan H. Gibcus
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Gibcus, J.H., Kok, K., Menkema, L. et al. High-resolution mapping identifies a commonly amplified 11q13.3 region containing multiple genes flanked by segmental duplications. Hum Genet 121, 187–201 (2007). https://doi.org/10.1007/s00439-006-0299-6

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