Mutation burden and I index for Detection of microsatellite instability in colorectal cancer by targeted next-generation sequencing

Publication date: Available online 31 October 2018Source: The Journal of Molecular DiagnosticsAuthor(s): Jeong Eun Kim, Sung-Min Chun, Yong Sang Hong, Kyu-pyo Kim, Sun Young Kim, Jihun Kim, Chang-Ohk Sung, Eun Jeong Cho, Tae Won Kim, Se Jin JangNext-generation sequencing (NGS) panels are widely used for defining tumor mutation profiles and determining treatment approaches. We performed targeted NGS with 382 genes in colorectal cancer with known microsatellite instability (MSI) status. After exclusion of germline alterations, load of somatic mutations and small insertion/deletion (indel) alterations were determined. In the test set, 79 patients with 41 microsatellite-stable (MSS) and 38 MSI tumors were included. There were 120 MSS and eight MSI-high tumors in the validation set. The number of somatic mutations of whole samples were distinguished into three groups; mutant functional polymerase epsilon catalytic subunit, MSI, and MSS tumors. Median number of somatic mutations and indel mutations in MSI tumors were higher. Indel mutation to whole mutation ratio (I index) was higher in MSI tumors. Considering hypermutation and low I index of polymerase epsilon catalytic subunit mutant tumors, with a somatic mutation load cut-off of ≥40 and I index of ≥9% were selected as the criteria for detecting MSI tumors with high sensitivity and specificity. With the analysis of alteration patterns of homopolymer genes, higher median number of homopolymer mutation in MSI tumors was observ...
Source: The Journal of Molecular Diagnostics - Category: Pathology Source Type: research