Generation of in situ sequencing based OncoMaps to spatially resolve gene expression profiles of diagnostic and prognostic markers in breast cancer.
Breast cancer
Diagnostic
Gene expression analysis
Prognostic
Tumor heterogeneity
Journal
EBioMedicine
ISSN: 2352-3964
Titre abrégé: EBioMedicine
Pays: Netherlands
ID NLM: 101647039
Informations de publication
Date de publication:
Oct 2019
Oct 2019
Historique:
received:
21
03
2019
revised:
05
09
2019
accepted:
05
09
2019
pubmed:
19
9
2019
medline:
21
3
2020
entrez:
19
9
2019
Statut:
ppublish
Résumé
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. 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. 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. 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.
Sections du résumé
BACKGROUND
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
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
RESULTS
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
CONCLUSIONS
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.
Identifiants
pubmed: 31526717
pii: S2352-3964(19)30607-3
doi: 10.1016/j.ebiom.2019.09.009
pmc: PMC6838368
pii:
doi:
Substances chimiques
Biomarkers, Tumor
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
212-223Informations de copyright
Copyright © 2019 The Authors. Published by Elsevier B.V. All rights reserved.
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