Predictive genetic biomarkers for the development of peritoneal metastases in colorectal cancer

Abstract Background Colorectal cancer (CRC) is a common cause of cancer related mortality, often due to metastases, of which peritoneal metastases (PM) have the worse outcome. Developing new treatments and searching ways to accomplish prevention of PM is therefore an important focus of clinical research. Metastases-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 specific DNA and RNA alterations in primary CRC tumors, which might be a predictive factor for the development of PM. Methods 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 by comprehensive genome sequencing (TSO500 analysis) to identify DNA alterations and RNA fusion transcripts in 523 genes and 55 genes, respectively. Results Thirty-eight samples were included for final analysis. Four M0 tumors and one PM tumor were microsatellite instable (MSI). 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. Conclusion BRAF p.V600E mutations were only present in PM patients with MSS tumors. Therefore, we believe greater attention should be paid to BRAF mutated tumors in relation to the development of metachronous PM.