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Mapping Spatial Genetic Landscapes in Tissue Sections through Microscale Integration of Sampling Methodology into Genomic Workflows


Voith von Voithenberg, Lena; Kashyap, Aditya; Opitz, Lennart; Aquino, Catharine; Sykes, Timothy; Nieser, Maike; Petrini, Lorenzo F T; Enrriquez Casimiro, Nadia; van Kooten, Xander F; Biskup, Saskia; Schlapbach, Ralph; Schraml, Peter; Kaigala, Govind V (2021). Mapping Spatial Genetic Landscapes in Tissue Sections through Microscale Integration of Sampling Methodology into Genomic Workflows. Small, 17(23):e2007901.

Abstract

In cancer research, genomic profiles are often extracted from homogenized macrodissections of tissues, with the histological context lost and a large fraction of material underutilized. Pertinently, the spatial genomic landscape provides critical complementary information in deciphering disease heterogeneity and progression. Microscale sampling methods such as microdissection to obtain such information are often destructive to a sizeable fraction of the biopsy sample, thus showing limited multiplexability and adaptability to different assays. A modular microfluidic technology is here implemented to recover cells at the microscale from tumor tissue sections, with minimal disruption of unsampled areas and tailored to interface with genome profiling workflows, which is directed here toward evaluating intratumoral genomic heterogeneity. The integrated workflow-GeneScape-is used to evaluate heterogeneity in a metastatic mammary carcinoma, showing distinct single nucleotide variants and copy number variations in different tumor tissue regions, suggesting the polyclonal origin of the metastasis as well as development driven by multiple location-specific drivers.

Abstract

In cancer research, genomic profiles are often extracted from homogenized macrodissections of tissues, with the histological context lost and a large fraction of material underutilized. Pertinently, the spatial genomic landscape provides critical complementary information in deciphering disease heterogeneity and progression. Microscale sampling methods such as microdissection to obtain such information are often destructive to a sizeable fraction of the biopsy sample, thus showing limited multiplexability and adaptability to different assays. A modular microfluidic technology is here implemented to recover cells at the microscale from tumor tissue sections, with minimal disruption of unsampled areas and tailored to interface with genome profiling workflows, which is directed here toward evaluating intratumoral genomic heterogeneity. The integrated workflow-GeneScape-is used to evaluate heterogeneity in a metastatic mammary carcinoma, showing distinct single nucleotide variants and copy number variations in different tumor tissue regions, suggesting the polyclonal origin of the metastasis as well as development driven by multiple location-specific drivers.

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Additional indexing

Item Type:Journal Article, refereed, original work
Communities & Collections:04 Faculty of Medicine > University Hospital Zurich > Institute of Pathology and Molecular Pathology
04 Faculty of Medicine > Functional Genomics Center Zurich
Dewey Decimal Classification:610 Medicine & health
Scopus Subject Areas:Life Sciences > Biotechnology
Physical Sciences > Biomaterials
Physical Sciences > General Chemistry
Physical Sciences > General Materials Science
Language:English
Date:June 2021
Deposited On:26 Aug 2021 16:42
Last Modified:25 Feb 2024 02:42
Publisher:Wiley-Blackwell Publishing, Inc.
ISSN:1613-6810
OA Status:Closed
Publisher DOI:https://doi.org/10.1002/smll.202007901
PubMed ID:33852760