The Association of DCC mRNA Alternative Splicing with Colorectal Cancer

Undergraduate Honors Thesis

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Citeable URL: https://scholar.colorado.edu/concern/undergraduate_honors_theses/1831ck330

Abstract

In as many as 70% of colorectal cancer cell (CRC) lines, there is a deletion of a chromosomal region, 18q21, which contains the Deleted in Colorectal Carcinoma (DCC) gene (Mehlen & Fearon, 2004). In adult cells, this single transmembrane receptor plays a role in both cell proliferation and cell death, thereby making it a promising candidate gene for the pathogenesis of colorectal cancer. It has been observed that alternative splicing of the DCC can affect its activity and that alternative splicing of DCC can be disrupted in cancer (Leggere et al., 2016; Reale et al., 1994). In this experiment, we sought to determine the association of alternative splicing of the DCC with colorectal cancer in cells without the deletion of the 18q21 region. By extracting RNA from 35 CRC cell lines and performing RT-PCR, we observed levels of the two DCC isoforms compared to normal adult colon cells. In this way, we determined that 29 of 35 CRC cell lines had altered splice patterns, indicating the alternative splicing may be related to colorectal cancer. These differences likely arose from genomic mutations in the Nova2 binding site, though additional research would be necessary to confirm this conjecture. Further research into this subject could shed light on the causes of colorectal cancer as well as perhaps one day aiding in diagnosis.

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