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Generation of in situ sequencing based OncoMaps to spatially resolve gene expression profiles of diagnostic and prognostic markers in breast cancer
BACKGROUND: Gene expression analysis of breast cancer largely relies on homogenized tissue samples. Due to the high degree of cellular and molecular heterogeneity of tumor tissues, bulk tissue-based analytical approaches can only provide very limited system-level information about different signalin...
Autores principales: | , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Elsevier
2019
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6838368/ https://www.ncbi.nlm.nih.gov/pubmed/31526717 http://dx.doi.org/10.1016/j.ebiom.2019.09.009 |
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author | Svedlund, Jessica Strell, Carina Qian, Xiaoyan Zilkens, Kilian J.C. Tobin, Nicholas P. Bergh, Jonas Sieuwerts, Anieta M. Nilsson, Mats |
author_facet | Svedlund, Jessica Strell, Carina Qian, Xiaoyan Zilkens, Kilian J.C. Tobin, Nicholas P. Bergh, Jonas Sieuwerts, Anieta M. Nilsson, Mats |
author_sort | Svedlund, Jessica |
collection | PubMed |
description | BACKGROUND: Gene expression analysis of breast cancer largely relies on homogenized tissue samples. Due to the high degree of cellular and molecular heterogeneity of tumor tissues, bulk tissue-based analytical approaches can only provide very limited system-level information about different signaling mechanisms and cellular interactions within the complex tissue context. METHODS: We describe an analytical approach using in situ sequencing (ISS), enabling highly multiplexed, spatially and morphologically resolved gene expression profiling. Ninety-one genes including prognostic and predictive marker profiles, as well as genes involved in specific cellular pathways were mapped within whole breast cancer tissue sections, covering luminal A/B-like, HER2-positive and triple negative tumors. Finally, all these features were combined and assembled into a molecular-morphological OncoMap for each tumor tissue. FINDINGS: Our in situ approach spatially revealed intratumoral heterogeneity with regard to tumor subtype as well as to the OncotypeDX recurrence score and even uncovered areas of minor cellular subpopulations. Since ISS-resolved molecular profiles are linked to their histological context, a deeper analysis of the core and periphery of tumor foci enabled identification of specific gene expression patterns associated with these morphologically relevant regions. INTERPRETATION: ISS generated OncoMaps represent useful tools to extend our general understanding of the biological processes behind tumor progression and can further support the identification of novel therapeutical targets as well as refine tumor diagnostics. FUND: Swedish Cancerfonden, UCAN, Vetenskapsrådet, Cancer Genomics Netherlands, Iris, Stig och Gerry Castenbäcks Stiftelse, BRECT, PCM Program, King Gustaf V Jubilee Fund, BRO, KI and Stockholm County Council, Alice Wallenberg Foundation. |
format | Online Article Text |
id | pubmed-6838368 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | Elsevier |
record_format | MEDLINE/PubMed |
spelling | pubmed-68383682019-11-12 Generation of in situ sequencing based OncoMaps to spatially resolve gene expression profiles of diagnostic and prognostic markers in breast cancer Svedlund, Jessica Strell, Carina Qian, Xiaoyan Zilkens, Kilian J.C. Tobin, Nicholas P. Bergh, Jonas Sieuwerts, Anieta M. Nilsson, Mats EBioMedicine Research paper BACKGROUND: Gene expression analysis of breast cancer largely relies on homogenized tissue samples. Due to the high degree of cellular and molecular heterogeneity of tumor tissues, bulk tissue-based analytical approaches can only provide very limited system-level information about different signaling mechanisms and cellular interactions within the complex tissue context. METHODS: We describe an analytical approach using in situ sequencing (ISS), enabling highly multiplexed, spatially and morphologically resolved gene expression profiling. Ninety-one genes including prognostic and predictive marker profiles, as well as genes involved in specific cellular pathways were mapped within whole breast cancer tissue sections, covering luminal A/B-like, HER2-positive and triple negative tumors. Finally, all these features were combined and assembled into a molecular-morphological OncoMap for each tumor tissue. FINDINGS: Our in situ approach spatially revealed intratumoral heterogeneity with regard to tumor subtype as well as to the OncotypeDX recurrence score and even uncovered areas of minor cellular subpopulations. Since ISS-resolved molecular profiles are linked to their histological context, a deeper analysis of the core and periphery of tumor foci enabled identification of specific gene expression patterns associated with these morphologically relevant regions. INTERPRETATION: ISS generated OncoMaps represent useful tools to extend our general understanding of the biological processes behind tumor progression and can further support the identification of novel therapeutical targets as well as refine tumor diagnostics. FUND: Swedish Cancerfonden, UCAN, Vetenskapsrådet, Cancer Genomics Netherlands, Iris, Stig och Gerry Castenbäcks Stiftelse, BRECT, PCM Program, King Gustaf V Jubilee Fund, BRO, KI and Stockholm County Council, Alice Wallenberg Foundation. Elsevier 2019-09-13 /pmc/articles/PMC6838368/ /pubmed/31526717 http://dx.doi.org/10.1016/j.ebiom.2019.09.009 Text en © 2019 The Authors http://creativecommons.org/licenses/by-nc-nd/4.0/ This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/). |
spellingShingle | Research paper Svedlund, Jessica Strell, Carina Qian, Xiaoyan Zilkens, Kilian J.C. Tobin, Nicholas P. Bergh, Jonas Sieuwerts, Anieta M. Nilsson, Mats Generation of in situ sequencing based OncoMaps to spatially resolve gene expression profiles of diagnostic and prognostic markers in breast cancer |
title | Generation of in situ sequencing based OncoMaps to spatially resolve gene expression profiles of diagnostic and prognostic markers in breast cancer |
title_full | Generation of in situ sequencing based OncoMaps to spatially resolve gene expression profiles of diagnostic and prognostic markers in breast cancer |
title_fullStr | Generation of in situ sequencing based OncoMaps to spatially resolve gene expression profiles of diagnostic and prognostic markers in breast cancer |
title_full_unstemmed | Generation of in situ sequencing based OncoMaps to spatially resolve gene expression profiles of diagnostic and prognostic markers in breast cancer |
title_short | Generation of in situ sequencing based OncoMaps to spatially resolve gene expression profiles of diagnostic and prognostic markers in breast cancer |
title_sort | generation of in situ sequencing based oncomaps to spatially resolve gene expression profiles of diagnostic and prognostic markers in breast cancer |
topic | Research paper |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6838368/ https://www.ncbi.nlm.nih.gov/pubmed/31526717 http://dx.doi.org/10.1016/j.ebiom.2019.09.009 |
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