Visualization of tumor heterogeneity by in situ padlock probe technology in colorectal cancer.
Tumor heterogeneity is considered a major cause for therapy resistance in colorectal cancer. Sub-populations of cells with different genetic alterations may exist in spatially distinct areas. Upon therapy, resistant sub-clones may enrich and ultimately lead to disease progression. Although ample dat...
| Publicado en: | Histochemistry & Cell Biology Vol. 148; no. 2; pp. 105 - 116 |
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| Autores principales: | , , , , , , , |
| Formato: | Journal Article |
| Publicado: |
Springer Nature
Aug2017
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| Acceso en línea: | Ver este registro en EBSCOhost |
| fields | @attributes: recordID: 1 pdfLink: plink: https://search.ebscohost.com/login.aspx?direct=true&db=ccm&AN=124071091&site=ehost-live header: @attributes: shortDbName: ccm uiTerm: 124071091 longDbName: CINAHL Complete uiTag: AN controlInfo: bkinfo: dissinfo: jinfo: jid: 09486143 NQI jtl: Histochemistry & Cell Biology issn: 09486143 maglogo: N pubinfo: dt: Aug2017 vid: 148 iid: 2 pid: 237 pub: Springer Nature place: New York, New York artinfo: ui: 124071091 144150632 10.1007/s00418-017-1557-5 124071091 ppf: 105 ppct: 11 formats: fmt: @attributes: type: P tig: atl: Visualization of tumor heterogeneity by in situ padlock probe technology in colorectal cancer. aug: au: El-Heliebi, Amin Kashofer, Karl Fuchs, Julia Jahn, Stephan Viertler, Christian Matak, Andrija Sedlmayr, Peter Hoefler, Gerald affil: Institute of Cell Biology, Histology and Embryology , Medical University of Graz , Harrachgasse 21/VII 8010 Graz Austria sug: ab: Tumor heterogeneity is considered a major cause for therapy resistance in colorectal cancer. Sub-populations of cells with different genetic alterations may exist in spatially distinct areas. Upon therapy, resistant sub-clones may enrich and ultimately lead to disease progression. Although ample data are available on tumors which are heterogeneous on a morphological level, only little is known about morphologically homogeneous tumors. We aimed to investigate if morphologically homogeneous colorectal cancer can harbor a heterogeneous genetic landscape. We chose to microdissect six morphologically homogeneous colorectal carcinomas into several areas and performed next-generation sequencing (NGS) to identify tumors with genetic heterogeneity. We then applied an mRNA-based in situ mutation detection technology based on padlock probes to localize and visualize mutations directly in the tumor tissue. In three out of six tumors, NGS revealed a high rate of variability of mutations between different tumor areas. We selected two cases for in situ mutation detection to visualize genetic heterogeneity. In situ mutation detection confirmed differences in mutant allele frequencies between different tumor areas of morphological homogeneous tumors. We conclude that genetic heterogeneity in morphologically homogeneous colorectal cancer is an observable, but underreported event. Our results illustrate the power of in situ mutation analysis to visualize genetic heterogeneity directly in tumor tissue. pubtype: Academic Journal doctype: Journal Article ougenre: Article language: English refInfo: holdings: @attributes: islocal: N |
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