Evolution of Mutational Landscape and Tumor Immune-Microenvironment in Liver Oligo-Metastatic Colorectal Cancer
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 evolutio...
| Main Authors: | , , , , , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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MDPI AG
2020-10-01
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| Series: | Cancers |
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| Online Access: | https://www.mdpi.com/2072-6694/12/10/3073 |
| _version_ | 1797550275871899648 |
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| author | 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 |
| author_facet | 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 |
| author_sort | Alessandro Ottaiano |
| collection | DOAJ |
| description | 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 <i>KRAS</i> and <i>SMAD4</i> alterations and a high granzyme-B+ T-cell infiltration when the disease did not progress. Conversely, gain in <i>KRAS</i>, <i>PIK3CA</i> and <i>SMAD4</i> 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. |
| first_indexed | 2024-03-10T15:27:01Z |
| format | Article |
| id | doaj.art-d7aad3cbf8f04c7ea6c7e22d9c473189 |
| institution | Directory Open Access Journal |
| issn | 2072-6694 |
| language | English |
| last_indexed | 2024-03-10T15:27:01Z |
| publishDate | 2020-10-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cancers |
| spelling | doaj.art-d7aad3cbf8f04c7ea6c7e22d9c4731892023-11-20T17:58:26ZengMDPI AGCancers2072-66942020-10-011210307310.3390/cancers12103073Evolution of Mutational Landscape and Tumor Immune-Microenvironment in Liver Oligo-Metastatic Colorectal CancerAlessandro Ottaiano0Michele Caraglia1Annabella Di Mauro2Gerardo Botti3Angela Lombardi4Jerome Galon5Amalia Luce6Luigi D’Amore7Francesco Perri8Mariachiara Santorsola9Fabienne Hermitte10Giovanni Savarese11Fabiana Tatangelo12Vincenza Granata13Francesco Izzo14Andrea Belli15Stefania Scala16Paolo Delrio17Luisa Circelli18Guglielmo Nasti19Department of Abdominal Oncology, SSD-Innovative Therapies for Abdominal Cancers, Istituto Nazionale Tumori di Napoli, IRCCS “G. Pascale”, Via M. Semmola, 80131 Naples, ItalyDepartment of Precision Medicine, University of Campania “L. Vanvitelli”, Via L. De Crecchio 7, 80138 Naples, ItalyDepartment of Pathology, Istituto Nazionale Tumori di Napoli, IRCCS “G. Pascale”, Via M. Semmola, 80131 Naples, ItalyDepartment of Pathology, Istituto Nazionale Tumori di Napoli, IRCCS “G. Pascale”, Via M. Semmola, 80131 Naples, ItalyDepartment of Precision Medicine, University of Campania “L. Vanvitelli”, Via L. De Crecchio 7, 80138 Naples, ItalyINSERM, Laboratory of Integrative Cancer Immunology, Equipe Labellisée Ligue Contre le Cancer, Sorbonne Université, Université Sorbonne Paris Cité, Université Paris Descartes, Université Paris Diderot, Centre de Recherche des Cordeliers, F-75006 Paris, FranceDepartment of Precision Medicine, University of Campania “L. Vanvitelli”, Via L. De Crecchio 7, 80138 Naples, ItalyAMES-Centro Polidiagnostico Strumentale, Srl, 80013 Naples, ItalyHead and Neck Cancer Medical Oncology Unit, Istituto Nazionale Tumori di Napoli, IRCCS “G. Pascale”, Via M. Semmola, 80131 Naples, ItalyDepartment of Abdominal Oncology, SSD-Innovative Therapies for Abdominal Cancers, Istituto Nazionale Tumori di Napoli, IRCCS “G. Pascale”, Via M. Semmola, 80131 Naples, ItalyHalioDx, 13288 Marseille, FranceAMES-Centro Polidiagnostico Strumentale, Srl, 80013 Naples, ItalyDepartment of Pathology, Istituto Nazionale Tumori di Napoli, IRCCS “G. Pascale”, Via M. Semmola, 80131 Naples, ItalyDepartment of Radiology, Istituto Nazionale Tumori di Napoli, IRCCS “G. Pascale”, Via M. Semmola, 80131 Naples, ItalyHepatic Surgery Unit, Istituto Nazionale Tumori di Napoli, IRCCS “G. Pascale”, Via M. Semmola, 80131 Naples, ItalyHepatic Surgery Unit, Istituto Nazionale Tumori di Napoli, IRCCS “G. Pascale”, Via M. Semmola, 80131 Naples, ItalyFunctional Genomics, Istituto Nazionale Tumori, IRCCS “G. Pascale”, Via M. Semmola, 80131 Naples, ItalyColorectal Abdominal Surgery Division, Istituto Nazionale Tumori, IRCCS “G. Pascale”, Via M. Semmola, 80131 Naples, ItalyAMES-Centro Polidiagnostico Strumentale, Srl, 80013 Naples, ItalyDepartment of Abdominal Oncology, SSD-Innovative Therapies for Abdominal Cancers, Istituto Nazionale Tumori di Napoli, IRCCS “G. Pascale”, Via M. Semmola, 80131 Naples, ItalyGenetic 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 <i>KRAS</i> and <i>SMAD4</i> alterations and a high granzyme-B+ T-cell infiltration when the disease did not progress. Conversely, gain in <i>KRAS</i>, <i>PIK3CA</i> and <i>SMAD4</i> 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.https://www.mdpi.com/2072-6694/12/10/3073colorectal cancerliver metastasesnext generation sequencing<i>KRAS</i><i>SMAD4</i> |
| spellingShingle | 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 Evolution of Mutational Landscape and Tumor Immune-Microenvironment in Liver Oligo-Metastatic Colorectal Cancer Cancers colorectal cancer liver metastases next generation sequencing <i>KRAS</i> <i>SMAD4</i> |
| title | Evolution of Mutational Landscape and Tumor Immune-Microenvironment in Liver Oligo-Metastatic Colorectal Cancer |
| title_full | Evolution of Mutational Landscape and Tumor Immune-Microenvironment in Liver Oligo-Metastatic Colorectal Cancer |
| title_fullStr | Evolution of Mutational Landscape and Tumor Immune-Microenvironment in Liver Oligo-Metastatic Colorectal Cancer |
| title_full_unstemmed | Evolution of Mutational Landscape and Tumor Immune-Microenvironment in Liver Oligo-Metastatic Colorectal Cancer |
| title_short | Evolution of Mutational Landscape and Tumor Immune-Microenvironment in Liver Oligo-Metastatic Colorectal Cancer |
| title_sort | evolution of mutational landscape and tumor immune microenvironment in liver oligo metastatic colorectal cancer |
| topic | colorectal cancer liver metastases next generation sequencing <i>KRAS</i> <i>SMAD4</i> |
| url | https://www.mdpi.com/2072-6694/12/10/3073 |
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