Molecular Characterization of Rhesus Colorectal Cancer: A Comparative Study with Human MMRd CRC

Colorectal cancer (CRC) is a leading cause of morbidity and mortality worldwide. In the United States alone, it remains the third most common cancer diagnosis, with approximately 15% of cases displaying Microsatellite Instability (MSI) secondary to Lynch Syndrome (LS) or somatic hypermethylation of the MLH1 promoter. Recent studies have highlighted the importance of molecular characterization in understanding the complexities of CRC. In this context, our research team employed cutting-edge systems biology tools to conduct a comprehensive analysis of gene set enrichment, consensus molecular subtyping, and somatic mutation profiling.

Using next-generation sequencing (NGS) technology, we analyzed a cohort of rhesus macaques from our institution that developed spontaneous mismatch repair deficient (MMRd) CRC. Notably, a significant proportion of these animals harbored pathogenic germline mutations in the MLH1 gene (c.1029C>G, p.Tyr343Ter). This observation underscores the importance of investigating the molecular mechanisms underlying CRC development and progression.

To gain deeper insights into the molecular characteristics of rhesus MMRd CRC, we employed a range of techniques, including PCR-based MSI testing, transcriptomics analysis, reduced-representation bisulfite sequencing (RRBS), and MLH1 DNA methylation profiling. Our study aimed to provide a detailed molecular characterization of rhesus CRC for cross-comparison with human MMRd CRC.

Our results demonstrate the power of systems biology approaches in elucidating the complex molecular mechanisms underlying CRC development and progression. The findings from this study have significant implications for our understanding of CRC pathogenesis and may inform the development of novel therapeutic strategies. Ultimately, this research aims to contribute to the advancement of personalized medicine for patients with MMRd CRC.

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