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Chromogenic detection of telomere lengths in situ aids the identification of precancerous lesions in the prostate

Telomeres are terminal chromosomal elements that are essential for the maintenance of genomic integrity. The measurement of telomere content provides useful diagnostic and prognostic information, and fluorescent methods have been developed for this purpose. However, fluorescent-based tissue assays a...

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Autores principales: Ertunc, Onur, Smearman, Erica, Zheng, Qizhi, Hicks, Jessica L., Brosnan-Cashman, Jacqueline A., Jones, Tracy, Gomes-Alexandre, Carolina, Trabzonlu, Levent, Meeker, Alan K., De Marzo, Angelo M., Heaphy, Christopher M.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Cold Spring Harbor Laboratory 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10104079/
https://www.ncbi.nlm.nih.gov/pubmed/37066381
http://dx.doi.org/10.1101/2023.04.04.535575
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author Ertunc, Onur
Smearman, Erica
Zheng, Qizhi
Hicks, Jessica L.
Brosnan-Cashman, Jacqueline A.
Jones, Tracy
Gomes-Alexandre, Carolina
Trabzonlu, Levent
Meeker, Alan K.
De Marzo, Angelo M.
Heaphy, Christopher M.
author_facet Ertunc, Onur
Smearman, Erica
Zheng, Qizhi
Hicks, Jessica L.
Brosnan-Cashman, Jacqueline A.
Jones, Tracy
Gomes-Alexandre, Carolina
Trabzonlu, Levent
Meeker, Alan K.
De Marzo, Angelo M.
Heaphy, Christopher M.
author_sort Ertunc, Onur
collection PubMed
description Telomeres are terminal chromosomal elements that are essential for the maintenance of genomic integrity. The measurement of telomere content provides useful diagnostic and prognostic information, and fluorescent methods have been developed for this purpose. However, fluorescent-based tissue assays are cumbersome for investigators to undertake, both in research and clinical settings. Here, a robust chromogenic in situ hybridization (CISH) approach was developed to visualize and quantify telomere content at single cell resolution in human prostate tissues, both frozen and formalin-fixed, paraffin-embedded (FFPE). This new assay (“Telo-CISH”) produces permanently stained slides that are viewable with a standard light microscope, thus avoiding the need for specialized equipment and storage. The assay is compatible with standard immunohistochemistry, thereby allowing simultaneous assessment of histomorphology, identification of specific cell types, and assessment of telomere status. In addition, Telo-CISH eliminates the problem of autofluorescent interference that frequently occurs with fluorescent-based methods. Using this new assay, we demonstrate successful application of Telo-CISH to help identify precancerous lesions in the prostate by the presence of markedly short telomeres specifically in the luminal epithelial cells. In summary, with fewer restrictions on the types of tissues that can be tested, and increased histologic information provided, the advantages presented by this novel chromogenic assay should extend the applicability of tissue-based telomere length assessment in research and clinical settings.
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spelling pubmed-101040792023-04-15 Chromogenic detection of telomere lengths in situ aids the identification of precancerous lesions in the prostate Ertunc, Onur Smearman, Erica Zheng, Qizhi Hicks, Jessica L. Brosnan-Cashman, Jacqueline A. Jones, Tracy Gomes-Alexandre, Carolina Trabzonlu, Levent Meeker, Alan K. De Marzo, Angelo M. Heaphy, Christopher M. bioRxiv Article Telomeres are terminal chromosomal elements that are essential for the maintenance of genomic integrity. The measurement of telomere content provides useful diagnostic and prognostic information, and fluorescent methods have been developed for this purpose. However, fluorescent-based tissue assays are cumbersome for investigators to undertake, both in research and clinical settings. Here, a robust chromogenic in situ hybridization (CISH) approach was developed to visualize and quantify telomere content at single cell resolution in human prostate tissues, both frozen and formalin-fixed, paraffin-embedded (FFPE). This new assay (“Telo-CISH”) produces permanently stained slides that are viewable with a standard light microscope, thus avoiding the need for specialized equipment and storage. The assay is compatible with standard immunohistochemistry, thereby allowing simultaneous assessment of histomorphology, identification of specific cell types, and assessment of telomere status. In addition, Telo-CISH eliminates the problem of autofluorescent interference that frequently occurs with fluorescent-based methods. Using this new assay, we demonstrate successful application of Telo-CISH to help identify precancerous lesions in the prostate by the presence of markedly short telomeres specifically in the luminal epithelial cells. In summary, with fewer restrictions on the types of tissues that can be tested, and increased histologic information provided, the advantages presented by this novel chromogenic assay should extend the applicability of tissue-based telomere length assessment in research and clinical settings. Cold Spring Harbor Laboratory 2023-04-06 /pmc/articles/PMC10104079/ /pubmed/37066381 http://dx.doi.org/10.1101/2023.04.04.535575 Text en https://creativecommons.org/licenses/by-nc-nd/4.0/This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License (https://creativecommons.org/licenses/by-nc-nd/4.0/) , which allows reusers to copy and distribute the material in any medium or format in unadapted form only, for noncommercial purposes only, and only so long as attribution is given to the creator.
spellingShingle Article
Ertunc, Onur
Smearman, Erica
Zheng, Qizhi
Hicks, Jessica L.
Brosnan-Cashman, Jacqueline A.
Jones, Tracy
Gomes-Alexandre, Carolina
Trabzonlu, Levent
Meeker, Alan K.
De Marzo, Angelo M.
Heaphy, Christopher M.
Chromogenic detection of telomere lengths in situ aids the identification of precancerous lesions in the prostate
title Chromogenic detection of telomere lengths in situ aids the identification of precancerous lesions in the prostate
title_full Chromogenic detection of telomere lengths in situ aids the identification of precancerous lesions in the prostate
title_fullStr Chromogenic detection of telomere lengths in situ aids the identification of precancerous lesions in the prostate
title_full_unstemmed Chromogenic detection of telomere lengths in situ aids the identification of precancerous lesions in the prostate
title_short Chromogenic detection of telomere lengths in situ aids the identification of precancerous lesions in the prostate
title_sort chromogenic detection of telomere lengths in situ aids the identification of precancerous lesions in the prostate
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10104079/
https://www.ncbi.nlm.nih.gov/pubmed/37066381
http://dx.doi.org/10.1101/2023.04.04.535575
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