e16381 Background: Colorectal cancers have been touted as the third most common cancer and the third leading cause of cancer death worldwide. Of these, rectal cancers often have a more favorable outcome, and are generally responsive to chemotherapy and radiation, due to metastasis limited to local tissues via lymphatics. However, in recent years, cases of rectal cancer with distant metastasis to the CNS have been noted at an urban community hospital serving a primarily Hispanic population in central New Jersey. Methods: We used genetic data from 51 patients at our local cancer center over 5 years to delineate risk factors associated with CNS metastasis. Of these patients, two had CNS metastasis with available tumor genetic information. We performed a gene enrichment analysis to determine phenotypic terms and molecular pathways associated with each gene set using Enrichr. Results: Of 51 patients, genetic data was available on 20, of which 18 had rectal cancer without CNS metastasis. Mutations involving 23 genes were found in this cohort, analysis of which found enrichment of the terms “Lynch Syndrome” and “Constitutional mismatch repair deficiency syndrome”, which are classically implicated in CRCs. In addition, enrichment of the terms “rectal cancer childhood”, “colorectal cancer childhood”, and “Familial colorectal cancer” were found. Of the two patients who had metastasis to the CNS, mutations involving 14 genes were found. Interestingly, both patients had mutations involving KRAS. Analysis of these genes found enrichment of the terms “pilomyxoid astrocytoma”, “giant cell glioblastoma” and “gliosarcoma”. Interestingly, common to both cohorts were the classic CRC-associated genes KRAS, APC and TP53, further solidifying their role in general CRCs. Conclusions: While this study is ongoing, preliminary data suggest that genetic analysis of tumors in patients with rectal cancer can determine whether a patient is susceptible to CNS metastasis. Given the heterogeneity of these cancers, further studies involving tumor and germ-line genetic analysis, which follow patients longitudinally may benefit in predicting which tumors are prone to CNS metastasis before they metastasize.