231 DNA and RNA alterations associated with colorectal peritoneal metastases: A systematic review INTRODUCTION Colorectal cancer (CRC) is the third most prevalent type of cancer worldwide and a common cause of morbidity and mortality, which is generally attributable to metastatic disease 1, 2. At initial diagnosis, almost one-fourth of patients with CRC present with synchronous metastases 2, 3. Liver metastases (LM) occur most frequently, followed by peritoneal metastases (PM) 2, 4. Colorectal PM are found in 5–15% of patients at primary diagnosis (synchronous PM) 2, 4-6]. One can also develop PM after curative resection of the primary tumor (metachronous PM), usually within the first 3 years after the primary diagnosis 3. Metachronous PM are reported in 4–12% of colon cancer patients and in 2–19% of rectal cancer patients 4, 6. However, the true incidence of PM might be underestimated. The preoperative diagnosis is mostly made by CT scan, but this has limited diagnostic accuracy for the assessment of the extent of PM 2, 6, 7. CRC patients with PM have a poor prognosis. Currently, the only potentially life-prolonging treatment option involves surgical debulking of all visible metastases (cytoreductive surgery; CRS) followed by Hyperthermic Intraperitoneal Chemotherapy (HIPEC). Only a highly selected group of patients are eligible for this intervention. Patients with a poor physical condition and/or a too extensive metastatic disease are generally excluded and will undergo palliative systemic treatment or best supportive care only 2, 8, 9. Without any treatment, the average life expectancy is 6 to 12 months after diagnosis 5, 8, 10. Recently, research has been ongoing to develop new treatment options for locally advanced CRC patients 11. Since these new treatment techniques could be invasive to a certain degree and be expensive, it would not be desirable to implement these routinely for all patients. A diagnostic tool able to identify patients who are at high risk of developing metachronous PM would allow targeted treatment in a preventive and/or curative setting 2. According to previous research, a molecular profile of the primary tumor might help identify patients who are at high risk. It is hypothesized that specific biomarkers identified in the primary tumor can be incorporated in a prediction tool to estimate the risk of distant metastatic spread 12, 13. In patients with synchronous PM, genetic alterations could be interesting to determine prognosis or to predict response to therapy. It is known that several pathogenic mutations occur during adenoma-to-carcinoma transformation in CRC. Important oncogenes are adenomatous polyposis coli (APC), tumor suppressor gene TP53, Kirsten rat sarcoma virus (KRAS), transforming growth factor beta (TGF-β), and phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha (PIK3CA) 14, 15. Recent data suggest mutations may also affect the metastatic dissemination of tumors 16. Different omics techniques, such as genomics (e.g., next-generation sequencing (NGS), polymerase chain reaction (PCR), pyrosequencing (PS), Sanger sequencing (SS)) and transcriptomics (e.g., NGS), could be used to elucidate DNA markers and RNA transcripts, respectively. Furthermore, individual omics techniques can be integrated into multi-omics 11
RkJQdWJsaXNoZXIy MTk4NDMw