title: The common fragile site genes CNTLN and LINGO2 are associated with increased genomic instability in different tumors
creator: Zahedi Hamedani, Sarah
subject: 570
subject: 570 Life sciences
description: Genomic instability is a characteristic of almost all human cancers. Most commonly, it may result from gross chromosomal changes, such as translocations, deletions and amplifications, which lead to chromosomal instability. Such chromosomal abnormalities are the consequence of DNA double-strand breaks (DSBs) which result from stalled replication forks formed within common fragile sites (CFSs). Based on several studies it is proposed that CFSs are prone to deletions and translocations in cancer cells and also instability-induced alterations in some CFS genes contribute to cancer development.  The short arm of chromosome 9 has been found to be involved in several types of tumors. Translocations and loss of heterozygosity (LOH) on 9p have been frequently reported in various cancers. In this thesis the overall rearrangement events on entire 9p and the impact of two 9p-located CFSs and their associated genes (FRA9G/CNTLN and FRA9C/LINGO2) on instability of the region were investigated. The analysis was performed on four tumor model types using high resolution array-based comparative genomic hybridization (CGH). A high percentage of the cell lines showed rearrangements on their 9p arm. Overall, three regions of breakpoint clusters were identified on 9p including the two CFSs (FRA9G/CNTLN, FRA9C/LINGO2) and the CDKN2A locus. Different patterns of alterations and distribution of breakpoints were observed in each tumor type. FRA9G/CNTLN and FRA9C/LINGO2 were frequently involved in genomic alterations of 9p, particulary in glioma/glioblastoma and neuroblastoma cells. Additionally, in three tumor types (glioma/glioblastoma, neuroblastoma and colon cancers) a significant number of breakages occurred in a region flanked by the two CFSs. Moreover, having the advantage of high-resolution aCGH, other genes of frequently damage were observed, leading to suggest them as novel candidates for tumor-susceptibility loci. All these results strongly indicate the association of FRA9G/CNTLN and FRA9C/LINGO2 to increased genomic instability of 9p in different tumor types. One important task to be explored in the future will be the causes and effects of dysfunction of these newly identified genes in tumor development. 
date: 2010
type: Dissertation
type: info:eu-repo/semantics/doctoralThesis
type: NonPeerReviewed
format: application/pdf
identifier: https://archiv.ub.uni-heidelberg.de/volltextserverhttps://archiv.ub.uni-heidelberg.de/volltextserver/11529/1/SarahZahedi_Dissertation.pdf
identifier: DOI:10.11588/heidok.00011529
identifier: urn:nbn:de:bsz:16-opus-115291
identifier:   Zahedi Hamedani, Sarah  (2010) The common fragile site genes CNTLN and LINGO2 are associated with increased genomic instability in different tumors.  [Dissertation]     
relation: https://archiv.ub.uni-heidelberg.de/volltextserver/11529/
rights: info:eu-repo/semantics/openAccess
rights: http://archiv.ub.uni-heidelberg.de/volltextserver/help/license_urhg.html
language: eng