Developments in the field of Cancer Epigenetics

The Dawn of a New Diagnostic Marker for Colorectal Cancer?

Submitted by: Kebaneilwe Lebani 41921706

School of Chemistry & Molecular Biosciences

University of Queensland

20 April 2009

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Colorectal cancer (CRC) incidences are high the world over. The US documents colorectal cancer as its second most prevalent cancer and China reports an increase in CRC incidence. Due to the high incidence and prevalence of cancers as a whole, research has increased efforts not only towards therapeutics but also towards diagnostic markers that can be used for early detection of cancer to improve therapeutic options and prognosis. A collaborative study undertaken by Zhang et al in 2008 entitled Epigenetic Inactivation of the Canonical Wnt Antagonist SRY-Box Containing Gene 17 in Colorectal Cancer brings to the fore a gene called Sox 17 that is involved in early development of CRC and has potential of serving as a marker for early colorectal carcinomas.

The promoter region of Sox 17 gene in CRC was found by Zhang et al, to be silenced by an epigenetic phenomenon and DNA hypermethylation was the mechanism through which the epigenetic changes occurred. The Sox 17 gene promoter in normal colorectal tissue is not methylated and the protein product of the Sox 17 gene has a tumour suppressive function that antagonizes the activity of a downstream pathway called the Wnt signaling pathway. Unidentified events that lead to the hypermethylation of the Sox 17 CpG Islands of the promoter region silence the gene, resulting in aberrant Wnt signaling and the development of carcinomas. Zhang et al documented that this process could be identified in 100% of stage I and II CRC. This epigenetic change coupled with genetic changes is what then drives the progression of CRC. Although the transcription repressive mechanism of the Sox 17 promoter requires further elucidation, its implication in early tumourigenesis makes it a suitable candidate as a novel marker for colorectal cancer.

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