Deciphering Elevated Microsatellite Alterations at Selected Tetra/Pentanucleotide Repeats, Microsatellite Instability, and Loss of Heterozygosity in Colorectal Cancers

Publication date: Available online 21 February 2018 Source:The Journal of Molecular Diagnostics Author(s): Yang Wang, Cindy L. Vnencak-Jones, Justin M. Cates, Chanjuan Shi Elevated microsatellite alterations at selected tetranucleotide repeats are common in colorectal cancers (CRCs). Its association with classic mono/dinucleotide microsatellite instability (MSI) is unknown. We assessed the stability of 13 tetranucleotide and three pentanucleotide repeat markers on both tumor and normal tissue from a cohort of 22 MSI-high (MSI-H) and 107 microsatellite stable (MSS) CRCs. When present, instability was observed at tetra/pentanucleotide repeats and defined as elevated microsatellite alterations at selected tetra/pentanucleotide repeats-high (EMASTP-H) (≥ 30% instability), EMASTP-low (<30% instability), and EMASTP-stable. EMASTP instability, including both high and low, was observed in 50 of 123 (41%) CRCs, including all MSI-H and 28 of 101 (28%) MSS tumors. MSI-H CRCs were more likely to be EMASTP-H compared to MSS tumors with EMASTP instability. Tetranucleotide markers, VWA and D13S317, were the two most frequently altered loci. Loss of heterozygosity (LOH) was more common in EMASTP-low/stable than in EMASTP-H CRCs. The frequency of LOH at three loci were different between EMASTP-low and EMASTP-stable tumors. In addition, right side, large tumor size, high tumor grade, and presence of Crohn’s-like reaction were significantly associated with EMASTP-H CRCs. Howeve...
Source: The Journal of Molecular Diagnostics - Category: Pathology Source Type: research