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Predictive Genetic Biomarkers for the Development of Peritoneal Metastases in Colorectal Cancer

Metastatic colorectal cancer (CRC) is a common cause of cancer-related mortality, of which peritoneal metastases (PMs) have the worse outcome. Metastasis-specific markers may help predict the spread of tumor cells and select patients for preventive strategies. This exploratory pilot study aimed to g...

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Autores principales: Heuvelings, Danique J. I., Wintjens, Anne G. W. E., Moonen, Laura, Engelen, Sanne M. E., de Hingh, Ignace H. J. T., Valkenburg-van Iersel, Liselot B., den Dulk, Marcel, Beckervordersandforth, Jan, Thijssen, Sharon G. M., Leunissen, Daphne J. G., Stassen, Laurents P. S., Keszthelyi, Daniel, Mujagic, Zlatan, Speel, Ernst-Jan M., Bouvy, Nicole D.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10454220/
https://www.ncbi.nlm.nih.gov/pubmed/37629011
http://dx.doi.org/10.3390/ijms241612830
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author Heuvelings, Danique J. I.
Wintjens, Anne G. W. E.
Moonen, Laura
Engelen, Sanne M. E.
de Hingh, Ignace H. J. T.
Valkenburg-van Iersel, Liselot B.
den Dulk, Marcel
Beckervordersandforth, Jan
Thijssen, Sharon G. M.
Leunissen, Daphne J. G.
Stassen, Laurents P. S.
Keszthelyi, Daniel
Mujagic, Zlatan
Speel, Ernst-Jan M.
Bouvy, Nicole D.
author_facet Heuvelings, Danique J. I.
Wintjens, Anne G. W. E.
Moonen, Laura
Engelen, Sanne M. E.
de Hingh, Ignace H. J. T.
Valkenburg-van Iersel, Liselot B.
den Dulk, Marcel
Beckervordersandforth, Jan
Thijssen, Sharon G. M.
Leunissen, Daphne J. G.
Stassen, Laurents P. S.
Keszthelyi, Daniel
Mujagic, Zlatan
Speel, Ernst-Jan M.
Bouvy, Nicole D.
author_sort Heuvelings, Danique J. I.
collection PubMed
description Metastatic colorectal cancer (CRC) is a common cause of cancer-related mortality, of which peritoneal metastases (PMs) have the worse outcome. Metastasis-specific markers may help predict the spread of tumor cells and select patients for preventive strategies. This exploratory pilot study aimed to gain more insight into genetic alterations in primary CRC tumors, which might be a predictive factor for the development of PM. Forty patients with T3 stage CRC were retrospectively divided in three groups: without metachronous metastases during 5-year follow-up (M0, n = 20), with metachronous liver metastases (LM, n = 10) and with metachronous PM (PM, n = 10). Patients with synchronous metastases were excluded. Primary formalin-fixed paraffin-embedded tumor samples were analyzed via comprehensive genome sequencing (TSO500 analysis) to identify DNA alterations and RNA fusion transcripts in 523 genes and 55 genes, respectively. Thirty-eight samples were included for final analysis. Four M0 tumors and one PM tumor were microsatellite instable. BRAF mutations were uniquely identified in three microsatellite-stable (MSS) PM tumors (37.5%, p = 0.010). RNA analysis showed an additional FAM198A-RAF1 fusion in one PM sample. BRAF p.V600E mutations were only present in PM patients with MSS tumors. Greater attention should be paid to BRAF-mutated tumors in relation to the development of metachronous PM.
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spelling pubmed-104542202023-08-26 Predictive Genetic Biomarkers for the Development of Peritoneal Metastases in Colorectal Cancer Heuvelings, Danique J. I. Wintjens, Anne G. W. E. Moonen, Laura Engelen, Sanne M. E. de Hingh, Ignace H. J. T. Valkenburg-van Iersel, Liselot B. den Dulk, Marcel Beckervordersandforth, Jan Thijssen, Sharon G. M. Leunissen, Daphne J. G. Stassen, Laurents P. S. Keszthelyi, Daniel Mujagic, Zlatan Speel, Ernst-Jan M. Bouvy, Nicole D. Int J Mol Sci Article Metastatic colorectal cancer (CRC) is a common cause of cancer-related mortality, of which peritoneal metastases (PMs) have the worse outcome. Metastasis-specific markers may help predict the spread of tumor cells and select patients for preventive strategies. This exploratory pilot study aimed to gain more insight into genetic alterations in primary CRC tumors, which might be a predictive factor for the development of PM. Forty patients with T3 stage CRC were retrospectively divided in three groups: without metachronous metastases during 5-year follow-up (M0, n = 20), with metachronous liver metastases (LM, n = 10) and with metachronous PM (PM, n = 10). Patients with synchronous metastases were excluded. Primary formalin-fixed paraffin-embedded tumor samples were analyzed via comprehensive genome sequencing (TSO500 analysis) to identify DNA alterations and RNA fusion transcripts in 523 genes and 55 genes, respectively. Thirty-eight samples were included for final analysis. Four M0 tumors and one PM tumor were microsatellite instable. BRAF mutations were uniquely identified in three microsatellite-stable (MSS) PM tumors (37.5%, p = 0.010). RNA analysis showed an additional FAM198A-RAF1 fusion in one PM sample. BRAF p.V600E mutations were only present in PM patients with MSS tumors. Greater attention should be paid to BRAF-mutated tumors in relation to the development of metachronous PM. MDPI 2023-08-15 /pmc/articles/PMC10454220/ /pubmed/37629011 http://dx.doi.org/10.3390/ijms241612830 Text en © 2023 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Heuvelings, Danique J. I.
Wintjens, Anne G. W. E.
Moonen, Laura
Engelen, Sanne M. E.
de Hingh, Ignace H. J. T.
Valkenburg-van Iersel, Liselot B.
den Dulk, Marcel
Beckervordersandforth, Jan
Thijssen, Sharon G. M.
Leunissen, Daphne J. G.
Stassen, Laurents P. S.
Keszthelyi, Daniel
Mujagic, Zlatan
Speel, Ernst-Jan M.
Bouvy, Nicole D.
Predictive Genetic Biomarkers for the Development of Peritoneal Metastases in Colorectal Cancer
title Predictive Genetic Biomarkers for the Development of Peritoneal Metastases in Colorectal Cancer
title_full Predictive Genetic Biomarkers for the Development of Peritoneal Metastases in Colorectal Cancer
title_fullStr Predictive Genetic Biomarkers for the Development of Peritoneal Metastases in Colorectal Cancer
title_full_unstemmed Predictive Genetic Biomarkers for the Development of Peritoneal Metastases in Colorectal Cancer
title_short Predictive Genetic Biomarkers for the Development of Peritoneal Metastases in Colorectal Cancer
title_sort predictive genetic biomarkers for the development of peritoneal metastases in colorectal cancer
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10454220/
https://www.ncbi.nlm.nih.gov/pubmed/37629011
http://dx.doi.org/10.3390/ijms241612830
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