Evolution of mutational landscape and tumor immune-microenvironment in liver oligo-metastatic colorectal cancer

Alessandro Ottaiano, Michele Caraglia, Annabella Di Mauro, Gerardo Botti, Angela Lombardi, Jerome Galon, Amalia Luce, Luigi D’amore, Francesco Perri, Mariachiara Santorsola, Fabienne Hermitte, Giovanni Savarese, Fabiana Tatangelo, Vincenza Granata, Francesco Izzo, Andrea Belli, Stefania Scala, Paolo Delrio, Luisa Circelli, Guglielmo Nasti

Research output: Contribution to journalArticlepeer-review

Abstract

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.

Original languageEnglish
Article number3073
Pages (from-to)1-16
Number of pages16
JournalCancers
Volume12
Issue number10
DOIs
Publication statusPublished - Oct 2020

Keywords

  • Colorectal cancer
  • KRAS
  • Liver metastases
  • Next generation sequencing
  • SMAD4

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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