Spatial allelic imbalance of BCL2 genes and chromosome 18 territories in nonneoplastic and neoplastic cervical squamous epithelium
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Several studies suggest a correlation between genome architecture and gene function. To elucidate mechanisms of gene positioning during cell differentiation and malignant transformation we investigated the nuclear positions of the BCL2 alleles and chromosome 18 territories in different layers of nonneoplastic cervical squamous epithelium and cervical squamous carcinomas in relation to gene expression. Fluorescence in situ hybridization and three-dimensional (3D) image analysis using tissue sections revealed that one BCL2 allele was located more peripherally than the other one in nuclei of the basal layer of nonneoplastic epithelium. During terminal cell differentiation the outer BCL2 allele showed a shift towards the nuclear center. In BCL2-expressing carcinomas the inner BCL2 allele was located more peripherally compared with the basal layer of nonneoplastic epithelium. Our results suggest a functional relevance of unequal allelic BCL2 gene positioning and support the hypothesis that transcriptional BCL2 activation is associated with BCL2 relocation towards the nuclear periphery.
KeywordsBCL2 gene domains Chromosome 18 territories 3D FISH Gene regulation Genome architecture Cervical cancer
The authors thank Prof. Dr. Rainer Siebert, Institute of Human Genetics, University Hospital Schleswig-Holstein, Kiel, Germany for providing the BCL2 FISH probe and Mrs. Lieselotte Bokla for excellent technical assistance. The authors are also indebted to Prof. Dr. Christoph Cremer, Kirchhoff Institute of Physics, University of Heidelberg for his continuous support and stimulating discussions. Funding of the German Ministry of Education and Research (FKZ 13N8350 “COMBO-FISH” and FKZ 01IG07015G “Services@MediGRID”) to Michael Hausmann is gratefully acknowledged. Finally, stimulations of Prof. Dr. Paul I. Prinz Zippl, University of Vienna, Austria, are acknowledged.
Conflict of interest statement
The authors declare that they have no conflict of interest.
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