The progression of colorectal cancer is strongly influenced by environmental and genetic
conditions. One of the key factors is tumor heterogeneity which is extensively studied
by cfDNA and bulk sequencing methods; however, we lack knowledge regarding its effects
at the single-cell level. Motivated by this, we aimed to employ an end-to-end single-cell
sequencing workflow from tissue-derived sample isolation to exome sequencing. Our
main goal was to investigate the heterogeneity patterns by laser microdissecting samples
from different locations of a tissue slide. Moreover, by studying healthy colon control,
tumor-associated normal, and colorectal cancer tissues, we explored tissue-specific
heterogeneity motifs. For completeness, we also compared the performance of the whole-exome
bulk, cfDNA, and single-cell sequencing methods based on variation at the level of
a single nucleotide.
