Different Types Of

Microsatellite instability was first described nearly simultaneously by three groups in 1993.[1-4]

There are two types of MSI in colorectal tumors: highly frequent MSI (MSI-H) is defined by a MSI frequency of >40% using a specified microsatellite marker panel. In contrast, tumors with a frequency of MSI of <40% are referred to as MSI-low tumors (MSI-L).[5] Mononucleotide markers such as BAT25, BAT26, and BAT40, which are almost monomorphic in germline DNA, show the highest mutation rates in tumors of the HNPCC spectrum. Alterations in these markers are associated very specifically with deficient MMR genes MSH2, MLH1, MSH6, and PMS2 in CRC. In contrast, the MSI-L phenotype is mostly restricted to dinucleotide markers and those with longer repeat units. A standardized, sensitive, and specific marker panel for detection of MSI in CRC was recently defined[5] and is currently recommended as the consensus marker panel for molecular HNPCC diagnostics in

The mutation spectrum (e.g., KRAS mutation, TP53 mutation, LOH at 5 q, 17 p, and 18 q) and the clinico-pathological features of MSI-L and MSS tumors are quite similar but differ from that in MSI-H cancers which show relatively open mutations in genes with coding repetitive sequences (e.g., TGFBR2, BAX). It has recently been suggested that MSI-L arises as a consequence of epigenetically silencing the O-6-methylguanine DNA methyltransferase (MGMT) gene through promoter hyper-methylation leading to promutagenic methylguanine ad-ducts which are not sufficiently eliminated and thereby overcharging the MMR system.[7]

Getting Started With Dumbbells

Getting Started With Dumbbells

The use of dumbbells gives you a much more comprehensive strengthening effect because the workout engages your stabilizer muscles, in addition to the muscle you may be pin-pointing. Without all of the belts and artificial stabilizers of a machine, you also engage your core muscles, which are your body's natural stabilizers.

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