High-resolution mapping identifies a commonly amplified 11q13.3 region containing multiple genes flanked by segmental duplications |
| |
Authors: | Johan H Gibcus Klaas Kok Lorian Menkema Mario A Hermsen Mirjam Mastik Philip M Kluin Jacqueline E van der Wal Ed Schuuring |
| |
Institution: | (1) Department of Pathology, University Medical Center Groningen, University of Groningen, PO Box 30001, 9700 RB Groningen, The Netherlands;(2) Department of Clinical Genetics, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands;(3) Department of Otolaryngology, Hospital Universitario Central de Asturias, Oviedo, Spain |
| |
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.
Electronic supplementary material Supplementary material is available in the online version of this article at and is accessible for authorized users. |
| |
Keywords: | |
本文献已被 PubMed SpringerLink 等数据库收录! |
|