A possible mechanistic role for microorganisms in the genesis of colorectal cancer.




Butcher, Lindsay D.

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Colorectal cancer (CRC) is the second leading cause of cancer-related deaths in the United States. An estimated over 140,000 people will be diagnosed with CRC and over 50,000 people will die in 2013. CRC tumors develop from a polyp but the initial cause of the chromosomal instability and mutations is unknown. Microorganisms are shown to be involved in other cancers so it is possible one may be involved with CRC. Identification of the organism may help prevention, diagnosis and treatment. Previous work in our lab identified the presence of JC virus (JCV) and increased expression of a protein in colorectal neoplasms compared to normal colon tissue. JCV is a polyomavirus that infects approximately 75% of the population. Polyomaviruses are DNA viruses and one of the proteins encoded in the genome is the T Antigen. The T Antigen protein is oncogenic and is capable of inactivating p53 and the pRb/p107/p130 protein families. While JCV remains in a latent state for the majority of those infected, we hypothesized that a disturbance to the immunological control allows for JCV to be active again and that the T Antigen may be involved in the development of colorectal neoplasms. Knowing the section T antigen protein that is most immunogenic and the ensuing immune response in patients with and without colon neoplasia will create a foundation to better understand the viral mechanism of action in the colon. Next generation sequencing allows for better identification of the colon microbiome. Using DNA from surgically removed colon tissues, we determined the presence of microorganisms in the colonic epithelium using next generation sequencing. One microorganism isolated was predominately in colon tumors and the adjacent normal tissue but was seen at much lower levels in adenomatous polyps or normal tissue without a tumor present. This microorganism may contribute to or be an indicator of CRC. Which microorganisms are present and the immune response to them will help identify their role in the development of CRC. Our studies evaluated the immune response to one virus and identified another possible microorganism that may be associated with colorectal carcinogenesis.



Colorectal cancer., JC virus., Immune response., Next generation sequencing., Microorganisms.