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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 territo-
ries 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 sec-
tions 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 differ-
entiation 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 tran-
scriptional BCL2 activation is associated with BCL2 relo-
cation towards the nuclear periphery.