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In situ mutation detection and visualization of intratumor heterogeneity for cancer research and diagnostics
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Genomics. Uppsala University, Science for Life Laboratory, SciLifeLab.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology. Uppsala University, Science for Life Laboratory, SciLifeLab.
Uppsala University, Science for Life Laboratory, SciLifeLab. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology.
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2013 (English)In: Oncotarget, ISSN 1949-2553, Vol. 4, no 12, 2407-2418 p.Article in journal (Refereed) Published
Abstract [en]

Current assays for somatic mutation analysis are based on extracts from tissue sections that often contain morphologically heterogeneous neoplastic regions with variable contents of normal stromal and inflammatory cells, obscuring the results of the assays. We have developed an RNA-based in situ mutation assay that targets oncogenic mutations in a multiplex fashion that resolves the heterogeneity of the tissue sample. Activating oncogenic mutations are targets for a new generation of cancer drugs. For anti-EGFR therapy prediction, we demonstrate reliable in situ detection of KRAS mutations in codon 12 and 13 in colon and lung cancers in three different types of routinely processed tissue materials. High-throughput screening of KRAS mutation status was successfully performed on a tissue microarray. Moreover, we show how the patterns of expressed mutated and wild-type alleles can be studied in situ in tumors with complex combinations of mutated EGFR, KRAS and TP53. This in situ method holds great promise as a tool to investigate the role of somatic mutations during tumor progression and for prediction of response to targeted therapy.

Place, publisher, year, edition, pages
2013. Vol. 4, no 12, 2407-2418 p.
National Category
Basic Medicine
Research subject
Pathology
Identifiers
URN: urn:nbn:se:uu:diva-222138PubMedID: 24280411OAI: oai:DiVA.org:uu-222138DiVA: diva2:710866
Note

Botling och Nilsson har delat sista författarskap.

Available from: 2014-04-08 Created: 2014-04-08 Last updated: 2014-04-09Bibliographically approved

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PubMedhttp://www.impactjournals.com/oncotarget/index.php?journal=oncotarget&page=article&op=view&path%5B%5D=1527

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Kiflemariam, SaraImgenberg-Kreuz, JulianaEdlund, KarolinaMicke, PatrickSundström, MagnusSjöblom, TobiasBotling, JohanNilsson, Mats

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Kiflemariam, SaraImgenberg-Kreuz, JulianaEdlund, KarolinaMicke, PatrickSundström, MagnusSjöblom, TobiasBotling, JohanNilsson, Mats
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GenomicsScience for Life Laboratory, SciLifeLabDepartment of Immunology, Genetics and PathologyMolecular and Morphological PathologyMolecular tools
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