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El-Heliebi, A; Kashofer, K; Fuchs, J; Jahn, SW; Viertler, C; Matak, A; Sedlmayr, P; Hoefler, G.
Visualization of tumor heterogeneity by in situ padlock probe technology in colorectal cancer.
Histochem Cell Biol. 2017; 148(2):105-115 Doi: 10.1007/s00418-017-1557-5 [OPEN ACCESS]
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Führende Autor*innen der Med Uni Graz
El-Heliebi Amin
Kashofer Karl
Co-Autor*innen der Med Uni Graz
Fuchs Julia
Höfler Gerald
Jahn Stephan
Matak Andrija
Sedlmayr Peter
Viertler Christian

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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.
Find related publications in this database (using NLM MeSH Indexing)
Cell Line, Tumor -
Colorectal Neoplasms - genetics
Colorectal Neoplasms - pathology
DNA Mutational Analysis -
Genetic Heterogeneity -
Humans -
Point Mutation - genetics

Find related publications in this database (Keywords)
In situ
Padlock probe
Tumor heterogeneity
Colorectal cancer
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