Clinical utility of quasimonomorphic variation range (QMVR) on the determination of microsatellite instability (MSI) status in Japanese patients (pts) with colorectal cancer (CRC): GI-SCREEN-CRC-MSI sub-study 01.

Abstract

TPS808 Background: The current analysis for the determination of Microsatellite Instability (MSI) status in tumor requires matched normal DNA as a reference. The Promega MSI panel included five monomorphic markers (NR-21, BAT-26, BAT-25, NR-24, and MONO-27) which were known to have few variant alleles in Caucasian as well as Japanese. Therefore, these markers might be able to determine the MSI status without matched normal DNA, although it is conceivable that Quasi-Monomorphic Variation Range (QMVR) in each ethnic group could be different. In our pilot study, the QMVR in 149 Japanese healthy individuals were 98.4-104.4 base pair (bp) in NR-21, 111.4-117.4 bp in BAT-26, 121.0-127.0 bp in BAT-25, 129.5-135.5 bp in NR-24, and 149.9-155.9 bp in MONO-27, respectively. Methods: This clinical evaluation study is to establish the QMVR in Japanese colorectal cancer (CRC) patients (pts) and to evaluate the clinical utility of the QMVR on the determination of MSI status without matched normal DNA. The primary endpoint is the concordance of MSI status between the standard method using DNA from tumor plus matched normal samples and testing method using DNA from only tumor samples. The new MSI kits including the Promega MSI panel were manufactured under the Quality Management System (QMS) for in vitro diagnostics (IVDs). As the decision algorithm, tumors exhibiting 2 or more markers outside the QMVR were classified as MSI-High, cases with 1 marker outside the QMVR were classified as MSI-Low, and those without any marker outside the QMVRs were classified as microsatellite stable (MSS). Planned enrollment will be 400 pts. Clinical trial information: UMIN000024144.