285 Predictive genetic biomarkers for the development of peritoneal metastases in colorectal cancer Figure 3. FISH analysis of the M0 sample harboring the TARSL2—NTRK3 fusion, showing isolated green and red signals confirming an NTRK3 gene rearrangement. DISCUSSION In this study, we performed an integrated pan-cancer oncology enrichment next-generation sequencing assay (TSO500 analysis) to assess DNA and RNA alterations in 523 and 55 genes, respectively, in primary colorectal adenocarcinomas with or without metachronous PM or LM. Our cohort showed a significant difference in differentiation grade when PM samples were compared to LM and M0 samples, and in the LM group for neoadjuvant treatment. Genetic analysis of all MSS tumors revealed that pathogenic BRAF exon 15 p.(V600E) mutations were exclusively identified in three RAS wildtype tumors with metachronous PM (37.5%, p value = 0.010). RNA sequencing identified a FAM198A-RAF1 fusion in an additional tumor with PM, as well as a TARSL2-NTRK3 fusion in a M0 sample. Patient Characteristics and Clinicopathological Variables We identified two clinicopathological characteristics that were significantly different between the three tumor groups. First, the PM group contained more poor/moderately differentiated tumors, while M0 and LM tumors were more often moderately differentiated. The latter was also shown in an extensive analysis of the association between metachronous PM and clinicopathological characteristics by Zhang et al. 26. Tumor location is not mentioned in this analysis, although another study reports that right-sided primary colorectal tumors are associated with PM 2. Only 22% of the PM tumors in our cohort were right sided. Second, the lowest tumor cell percentages were observed in the LM group, which may be explained by the fact that in this group, more patients received neoadjuvant treatment via chemoradiation 12
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