%0 Journal Article
%T Microsatellite Instability in Sarcoma: Fact or Fiction?
%A Michael J. Monument
%A Stephen L. Lessnick
%A Joshua D. Schiffman
%A Rl. Tx. Randall
%J ISRN Oncology
%D 2012
%R 10.5402/2012/473146
%X Microsatellite instability (MSI) is a unique molecular abnormality, indicative of a deficient DNA mismatch repair (MMR) system. Described and characterized in the colorectal cancer literature, the MSI-positive phenotype is predictive of disease susceptibility, pathogenesis, and prognosis. The clinical relevance of MSI in colorectal cancer has inspired similar inquisition within the sarcoma literature, although unfortunately, with very heterogeneous results. Evolving detection techniques, ill-defined sarcoma-specific microsatellite loci and small study numbers have hampered succinct conclusions. The literature does suggest that MSI in sarcoma is observed at a frequency similar to that of sporadic colorectal cancers, although there is little evidence to suggest that MSI-positive tumors share distinct biological attributes. Emerging evidence in Ewing sarcoma has demonstrated an intriguing mechanistic role of microsatellite DNA in the activation of key EWS/FLI-target genes. These findings provide an alternative perspective to the biological implications of microsatellite instability in sarcoma and warrant further investigation using sophisticated detection techniques, sensitive microsatellite loci, and appropriately powered study designs. 1. The Essence of Microsatellite DNA The biological precedence of tandem nucleotide repeats scattered throughout the human genome has intrigued scientific inquiry since these genetic elements were first characterized in the early 1980s. More precisely, the term microsatellite DNA refers to tandem iterations of simple sequence motifs dispersed throughout the genome. The majority of microsatellite DNA is comprised of mono-, di-, tri- and tetra-nucleotide repeats, and these repetitive elements constitute ~3% of the human genome [1]. Current estimates suggest that there are approximately one million microsatellite loci within the human genome, and the vast majority of these sequences are situated within noncoding regions such as intronic and intergenic segments. Consequently, microsatellite DNA has been long regarded as ˇ°junk DNAˇ± with a poorly understood biological function. The repetitive nature of microsatellite DNA renders it more susceptible to mutagenesis during DNA replication and furthermore, the lack of evolutionary pressure on these noncoding regions has licensed an impressive rate of microsatellite polymorphisms in the human population overtime. Compared to coding regions of the genome, microsatellite loci are genetically diverse, characterized by high heterozygosity indices and numerous alleles for any given loci
%U http://www.hindawi.com/journals/isrn.oncology/2012/473146/