Genetic trajectory and immune microenvironment of lung-specific oligometastatic colorectal cancer

Alessandro Ottaiano (1) , Luisa Circelli , Angela Lombardi (2) , Stefania Scala (1) , Nicola Martucci (1) , Jerome Galon (3) , Manuela Buonanno (4) , Giosuè Scognamiglio (1) , Gerardo Botti (1) , Fabienne Hermitte , Giovanni Savarese , Luigi d'Amore , Fabiana Tatangelo (1) , Annabella Di Mauro (1) , Giuseppina Liguori (1) , Anna Maria Trotta (1) , Maria Napolitano (1) , Monica Capozzi (1) , Salvatore Tafuto (1) , Francesco Perri (1) , Antonello La Rocca (1) , Michele Caraglia (2) , Guglielmo Nasti (1)

1 IRCCS - Istituti di Ricovero e Cura a Carattere Scientifico
2 University of the Study of Campania Luigi Vanvitelli
3 CRC (UMR_S_1138 / U1138) - Centre de Recherche des Cordeliers
4 CUMC - Columbia University Medical Center

Genetics and immunologic dynamics pushing the evolution of colorectal cancer (CRC) from the primary tumor to the metastases are largely unknown; cancer heterogeneity makes challenging both therapy and mechanistic studies. We selected patients developing CRC with lung-limited metastatic disease as only illness during their life in order to find any relevant genotype-phenotype relationship. Analysis of 523 cancer-relevant genes and of immune cells infiltration in primary and metastatic tissues revealed atypical genomic trajectories (TMB decrease, KRAS and SMAD4 regressive mutations), specific genetic events (ERBB2 point mutations) and scarce T-cell infiltration. These insights provide novel information in oligometastatic CRC biology and new perspectives for cancer monitoring and anti-cancer therapeutic strategies.

Domaines: Sciences du Vivant [q-bio]

Alessandro Ottaiano, Luisa Circelli, Angela Lombardi, Stefania Scala, Nicola Martucci, et al.. Genetic trajectory and immune microenvironment of lung-specific oligometastatic colorectal cancer. Cell Death and Disease, 2020, 11 (4), pp.275. ⟨10.1038/s41419-020-2480-6⟩. ⟨hal-03188069⟩