Prevalence and implications of elevated microsatellite alterations at selected tetranucleotides in cancer

Abstract

Elevated microsatellite alterations at selected tetranucleotides (EMAST), a variation of microsatellite instability (MSI), has been reported in a variety of malignancies (e.g., neoplasias of the lung, head and neck, colorectal region, skin, urinary tract and reproductive organs). EMAST is more prominent at organ sites with potential external exposure to carcinogens (e.g., head, neck, lung, urinary bladder and colon), although the specific molecular mechanisms leading to EMAST remain elusive. Because it is often associated with advanced stages of malignancy, EMAST may be a consequence of rapid cell proliferation and increased mutagenesis. Moreover, defects in DNA mismatch repair enzyme complexes, TP53 mutation status and peritumoural inflammation involving T cells have been described in EMAST tumours. At various tumour sites, EMAST and high-frequency MSI share no clinicopathological features or molecular mechanisms, suggesting their existence as separate entities. Thus EMAST should be explored, because its presence in human cells may reflect both increased risk and the potential for early detection. In particular, the potential use of EMAST in prognosis and prediction may yield novel types of therapeutic intervention, particularly those involving the immune system. This review will summarise the current information concerning EMAST in cancer to highlight the knowledge gaps that require further research.

Elevated microsatellite alterations at selected tetranucleotides in early‐stage colorectal cancers with and without high‐frequency microsatellite instability: same, same but different?

“…We found a significantly lower prevalence of EMAST in our sample (23%) when compared with the majority of the studies available in the literature, reporting EMAST frequencies in CRC ranging between 33% and 64.8% . As previously reviewed , such variation could be due to the type and number of markers and the thresholds used in EMAST analyses, with the highest (60% and over) frequencies reported by groups using a less stringent approach to define EMAST . The degree of overlap between MSI cases and EMAST (77% in this study), is in line with studies that report between 67% and 100% overlap, and thus, the selected cohort should be within the range of variation as reported elsewhere in the literature.…”

<i>Fusobacterium nucleatum</i> Infection in Colorectal Cancer: Linking Inflammation, DNA Mismatch Repair and Genetic and Epigenetic Alterations

“…Although MSI-H is caused by the functional loss of MMR proteins, the etiology of MSI-L and the distinction between MSI-L and MSS CRC remained unclear until recently (10,28). Another type of microsatellite alteration, termed EMAST, where insertion/deletion mutations in the loci with tetra-nucleotide but not with mono- and/or dinucleotide repeats, were recognized as a component of CRC (32,33). MSI-L and EMAST have been observed in many human cancers (10,32).…”

“…Another type of microsatellite alteration, termed EMAST, where insertion/deletion mutations in the loci with tetra-nucleotide but not with mono- and/or dinucleotide repeats, were recognized as a component of CRC (32,33). MSI-L and EMAST have been observed in many human cancers (10,32). Haugen et al examined the frequency of EMAST in CRC, its relationship to MSI-L and its possible causes (33).…”

Microsatellite Alterations With Allelic Loss at 9p24.2 Signify Less-Aggressive Colorectal Cancer Metastasis

“…In addition to MSI defined by the NCI markers, another type of mutation at microsatellite loci has been observed in human cancers including CRC (16). Among non-MSI-H CRC, some tumors show instability at loci with tetra-nucleotide repeats containing [AAAG] or [AGAT] but not at loci with mononucleotide repeats (17, 18, 19, 20). This type of microsatellite instability is called EMAST, for e levated m icrosatellite a lterations at s elected t etra-nucleotide repeats.…”