Medizinische Universität Graz Austria/Österreich - Forschungsportal - Medical University of Graz
Gewählte Publikation:
SHR Neuro Krebs Kardio Lipid Stoffw Microb
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
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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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- Abstract:
- 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
- NGS
- Colorectal cancer