Genetic dynamics underlying
cancer progression are largely unknown and several genes involved in highly prevalent illnesses (e.g.,
hypertension,
obesity, and diabetes) strongly concur to
cancer phenotype heterogeneity. To study genotype-phenotype relationships contributing to the mutational evolution of
colorectal cancer (CRC) with a focus on liver
metastases, we performed genome profiling on
tumor tissues of CRC patients with liver metastatic disease and no co-morbidities. We studied 523
cancer-related genes and
tumor-immune microenvironment characteristics in primary and matched metastatic tissues. We observed a loss of KRAS and SMAD4 alterations and a high
granzyme-B+ T-cell infiltration when the disease did not progress. Conversely, gain in KRAS, PIK3CA and SMAD4 alterations and scarce
granzyme-B+ T-cells infiltration were observed when the
tumor evolved towards a poly-metastatic spread. These findings provide novel insights into the identification of
tumor oligo-metastatic status, indicating that some genes are on a boundary line between these two clinical settings (oligo- vs. poly-metastatic CRC). We speculate that the identification of these genes and modification of their evolution could be a new approach for anti-
cancer therapeutic strategies.