TY - JOUR
T1 - Predictive Genetic Biomarkers for the Development of Peritoneal Metastases in Colorectal Cancer
AU - Heuvelings, Danique J. I.
AU - Wintjens, Anne G. W. E.
AU - Moonen, Laura
AU - Engelen, Sanne M. E.
AU - de Hingh, Ignace H. J. T.
AU - Valkenburg-van Iersel, Liselot B.
AU - den Dulk, Marcel
AU - Beckervordersandforth, Jan
AU - Thijssen, Sharon G. M.
AU - Leunissen, Daphne J. G.
AU - Stassen, Laurents P. S.
AU - Keszthelyi, Daniel
AU - Mujagic, Zlatan
AU - Speel, Ernst-Jan M.
AU - Bouvy, Nicole D.
PY - 2023/8/1
Y1 - 2023/8/1
N2 - 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.
AB - 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.
KW - colorectal cancer
KW - peritoneal metastases
KW - biomarkers
KW - genetic mutations
KW - next generation sequencing
KW - CYTOREDUCTIVE SURGERY
KW - MOLECULAR BIOMARKERS
KW - BRAF MUTATION
KW - CARCINOMATOSIS
KW - PROGNOSIS
KW - SURVIVAL
KW - MARKER
KW - IMPACT
KW - RAS
KW - CLASSIFICATION
U2 - 10.3390/ijms241612830
DO - 10.3390/ijms241612830
M3 - Article
SN - 1661-6596
VL - 24
JO - International Journal of Molecular Sciences
JF - International Journal of Molecular Sciences
IS - 16
M1 - 12830
ER -