caa a22 4500 397573340 CHVBK 20180308164847.0 cr unu---uuuuu 161202e199602 xx s 000 0 eng 10.1093/hmg/5.2.187 doi (NATIONALLICENCE)oxford-10.1093/hmg/5.2.187 FRA3B Extends Over a Broad Region and Contains a Spontaneous HPV16 Integration Site: Direct Evidence for the Coincidence of Viral Integration Sites and Fragile Sites [Elektronische Daten] [Charles M. Wilke, Bryan K. Hall, Ann Hoge, William Paradee, David I. Smith, Thomas W. Glover] The common fragile site at 3p14.2 (FRA3B) is the most sensitive site on normal human chromosomes for the formation of gaps and breaks when DNA replication is perturbed by aphidicolin or folate stress. Although rare fragile sites are known to arise through the expansion of CCG repeats, the mechanism responsible for common fragile sites is unknown. Beyond being a basic component of chromosome structure, no biological effects of common fragile sites have been convincingly shown, although suggestions have been made that breakage and recombination at these sites may sometimes be mechanistically involved in deletions observed in many tumors and in constitutional deletions. In an observation related to the high rate of recombination at fragile sites, a number of studies have shown a statistical association between the integration of transforming DNA viruses and chromosomal fragile sites. Using FISH analysis we recently identified a 1.3 Mb YAC spanning both FRA3B and the t(3,8) translocation associated with hereditary RCC. Here we report the further localization of FRA3B within this YAC. Using lambda subclones of the YAC as FISH probes, gaps and breaks were found to occur over a broad region of at least 50 kb. Neither CCG nor CAG repeats were found in this region suggesting a different mechanism for fragility than seen with rare fragile sites. We further show that an area of frequent gaps and breaks within FRA3B, defined by a lambda contig, coincides with a previously characterized site of HPV16 integration in a primary cervical carcinoma. The HPV16 integration event gave rise to a short chromosomal deletion limited to the local FRA3B region within 3p14.2. Interestingly, 3p14.2 lies within the smallest commonly deleted region of 3p in cervical cancers, which are often HPV16 associated. To our knowledge this is the first molecular characterization of an in vivo viral integration event within a confirmed fragile site region, supporting previous cytogenetic observations linking viral integration sites and fragile sites. © 1996 Oxford University Press Wilke Charles M. Department of Pediatrics and Department of Human Genetics, University of Michigan, 2818 MS II 0618, Ann Arbor, MI 48109, USA aut Hall Bryan K. Department of Pediatrics and Department of Human Genetics, University of Michigan, 2818 MS II 0618, Ann Arbor, MI 48109, USA aut Hoge Ann Department of Pediatrics and Department of Human Genetics, University of Michigan, 2818 MS II 0618, Ann Arbor, MI 48109, USA aut Paradee William Departments of Molecular Biology, Genetics and Internal Medicine, Wayne State University School of Medicine, 540 East Canfield, Detroit, MI 48201, USA aut Smith David I. Departments of Molecular Biology, Genetics and Internal Medicine, Wayne State University School of Medicine, 540 East Canfield, Detroit, MI 48201, USA aut Glover Thomas W. Department of Pediatrics and Department of Human Genetics, University of Michigan, 2818 MS II 0618, Ann Arbor, MI 48109, USA aut Human Molecular Genetics Oxford University Press 5/2(1996-02), 187-195 0964-6906 5:2<187 1996 5 hmg https://doi.org/10.1093/hmg/5.2.187 text/html Onlinezugriff via DOI 1 research-article jats NATIONALLICENCE 856 40 https://doi.org/10.1093/hmg/5.2.187 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Wilke Charles M. Department of Pediatrics and Department of Human Genetics, University of Michigan, 2818 MS II 0618, Ann Arbor, MI 48109, USA aut NATIONALLICENCE 700 1- Hall Bryan K. Department of Pediatrics and Department of Human Genetics, University of Michigan, 2818 MS II 0618, Ann Arbor, MI 48109, USA aut NATIONALLICENCE 700 1- Hoge Ann Department of Pediatrics and Department of Human Genetics, University of Michigan, 2818 MS II 0618, Ann Arbor, MI 48109, USA aut NATIONALLICENCE 700 1- Paradee William Departments of Molecular Biology, Genetics and Internal Medicine, Wayne State University School of Medicine, 540 East Canfield, Detroit, MI 48201, USA aut NATIONALLICENCE 700 1- Smith David I. Departments of Molecular Biology, Genetics and Internal Medicine, Wayne State University School of Medicine, 540 East Canfield, Detroit, MI 48201, USA aut NATIONALLICENCE 700 1- Glover Thomas W. Department of Pediatrics and Department of Human Genetics, University of Michigan, 2818 MS II 0618, Ann Arbor, MI 48109, USA aut NATIONALLICENCE 773 0- Human Molecular Genetics Oxford University Press 5/2(1996-02), 187-195 0964-6906 5:2<187 1996 5 hmg Metadata rights reserved CC BY-NC-4.0 http://creativecommons.org/licenses/by-nc/4.0 nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-oxford