Cervical carcinoma-associated fibroblasts are DNA diploid and do not show evidence for somatic genetic alterationsReport as inadecuate




Cervical carcinoma-associated fibroblasts are DNA diploid and do not show evidence for somatic genetic alterations - Download this document for free, or read online. Document in PDF available to download.

Cellular Oncology

, Volume 34, Issue 6, pp 553–563

First Online: 01 November 2011Accepted: 05 September 2011DOI: 10.1007-s13402-011-0061-5

Cite this article as: Corver, W.E., ter Haar, N.T., Fleuren, G.J. et al. Cell Oncol. 2011 34: 553. doi:10.1007-s13402-011-0061-5

Abstract

BackgroundCancer-associated fibroblasts CAFs have been recognized as important contributors to cancer development and progression. However, opposing evidence has been published whether CAFs, in addition to epigenetic, also undergo somatic genetic alterations and whether these changes contribute to carcinogenesis and tumour progression.

MethodsWe combined multiparameter DNA flow cytometry, flow-sorting and 6K SNP-arrays to study DNA aneuploidy, % S-phase, loss of heterozygosity LOH and copy number alterations CNAs in cervical cancer-associated stromal cell fractions n = 57 from formalin-fixed, paraffin-embedded FFPE samples. Tissue sections were examined for the presence of CAFs. Microsatellite analysis was used to confirm LOH findings.

ResultsSmooth muscle actin and vimentin immunohistochemistry verified the presence of CAFs in all cases tested. However, we found no evidence for DNA aneuploidy, somatic genetic alterations in the vimentin-positive stromal cell fractions of any samples, while high frequencies of DNA content abnormalities 43-57 and substantial numbers of CNAs and LOH were identified in the keratin-positive epithelial cell fractions. LOH hot-spots on chromosomes 3p, 4p and 6p found were confirmed by microsatellite analysis.

ConclusionFrom our study we conclude that stromal cell fractions from cervical carcinomas are DNA diploid, have a genotype undistinguishable from patient-matched normal tissue and are genetically stable. Using flow cytometry and SNP-arrays, stromal genetic changes do not seem to play a role during cervical carcinogenesis and progression. In addition, the stromal cell fraction of cervical carcinomas can be used as reference allowing large retrospective studies of archival FFPE tissues for which no normal reference tissue is available.

KeywordsCervical cancer Formalin-fixed, paraffin-embedded Carcinoma-associated fibroblast Vimentin Smooth-muscle actin Fluorescence activated cell sorter SNP-array Electronic supplementary materialThe online version of this article doi:10.1007-s13402-011-0061-5 contains supplementary material, which is available to authorized users.

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Author: Willem Ernst Corver - Natalja Tatjana ter Haar - Gert Jan Fleuren - Jan Oosting

Source: https://link.springer.com/







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