Molecular profiling of colon tumors: the search for clinically relevant biomarkers of progression, prognosis, therapeutics, and predisposition.
Review
Overview
abstract
If properly translated to clinical use, our knowledge about biomarkers may lead to a more effective way of combating colorectal cancer (CRC). Biomarkers are biomolecular, genetic, or cytogenetic attributes indicative of the disease's progression, predisposition, prognosis, or therapeutic options. For CRC, these include chromosomal instability, mutations in KRAS and TP53, loss of 18q, and elevated level of carcinoembryonic antigen (CEA), which are all associated with poor prognosis. The prognostic significance of 18q loss can be attributed to reduced expression of SMAD4, or DCC, although the chromosomal arm is actually heavily populated by genes whose downregulation correlate to worse survival. Potentially, identification of prognostic biomarkers can help the oncologist decide whether adjuvant chemotherapy is necessary after surgery. Testing for therapeutic biomarkers can be necessary if targeted therapeutics are being considered. The identification of highly penetrant predisposition markers (such as mutations in APC and MLH1) can be a lifesaver for carrier individuals, who would then have to undergo colonoscopy at an earlier age. Even sporadic CRCs may have some hereditary components, according to recent studies. Genome-wide association studies (using SNP arrays) showed that polymorphisms of certain genes can have subtle influence on CRC predisposition. Our own SNP array-based analysis suggested that long stretches of germline homozygosity (autozygosity), indicative of consanguinity, may also factor in CRC predisposition.
