Lin E.I.LI-HUI TSENGGocke C.D.Reil S.Le D.T.Azad N.S.Eshleman J.R.2022-03-102022-03-1020151949-2553https://www.scopus.com/inward/record.uri?eid=2-s2.0-84951858024&doi=10.18632%2foncotarget.5997&partnerID=40&md5=b28eec57c1d3dea20f9a02c670a9e694https://scholars.lib.ntu.edu.tw/handle/123456789/597105Microsatellite instability (MSI) is caused by defective mismatch repair in 15-20% of colorectal cancers (CRCs). Higher mutation loads in tumors with mismatch repair deficiency can predict response to pembrolizumab, an anti-programmed death 1 (PD-1) immune checkpoint inhibitor. We analyzed the mutations in 113 CRCs without MSI (MSS) and 29 CRCs with MSI-High (MSI-H) using the 50-gene AmpliSeq cancer panel. Overall, MSI-H CRCs showed significantly higher mutations than MSS CRCs, including insertion/deletion mutations at repeat regions. MSI-H CRCs showed higher incidences of mutations in the BRAF, PIK3CA, and PTEN genes as well as mutations in the receptor tyrosine kinase families. While the increased mutations in BRAF and PTEN in MSI-H CRCs are well accepted, we also support findings of mutations in the mTOR pathway and receptor tyrosine kinase family genes. MSS CRCs showed higher incidences of mutations in the APC, KRAS and TP53 genes, confirming previous findings. NGS assays may be designed to detect driver mutations for targeted therapeutics and to identify tumors with high mutation loads for potential treatment with immune checkpoint blockade therapies. Further studies may be warranted to elucidate potential targeted therapeutics against mutations in the mTOR pathway and the receptor tyrosine kinase family in MSI-H CRCs as well as the benefit of anti-PD-1 immunotherapy in hypermutated MSS CRCs or other cancers.Colorectal cancer; Microsatellite instability; MTOR pathway; Mutation profiling; PTEN[SDGs]SDG3APC protein; B Raf kinase; K ras protein; phosphatidylinositol 3,4,5 trisphosphate 3 phosphatase; protein p53; protein tyrosine kinase; APC protein; APC protein, human; B Raf kinase; KRAS protein, human; MTOR protein, human; phosphatidylinositol 3 kinase; phosphatidylinositol 3,4,5 trisphosphate 3 phosphatase; PIK3CA protein, human; protein p21; protein p53; PTEN protein, human; target of rapamycin kinase; adult; aged; APC gene; Article; BRAF gene; cancer incidence; carcinogenesis; colorectal cancer; controlled study; disease activity; female; gene deletion; gene insertion; gene mutation; gene targeting; human; major clinical study; male; microsatellite instability; molecular dynamics; molecular pathology; mutational analysis; oncogene; oncogene K ras; PI3KCA gene; promoter region; protein determination; protein function; PTEN gene; receptor tyrosine kinase gene; short tandem repeat; signal transduction; tumor suppressor gene; very elderly; colorectal tumor; dna mutational analysis; gene frequency; genetics; high throughput sequencing; mutation; procedures; Adenomatous Polyposis Coli Protein; Colorectal Neoplasms; DNA Mutational Analysis; Gene Frequency; High-Throughput Nucleotide Sequencing; Humans; Microsatellite Instability; Mutation; Phosphatidylinositol 3-Kinases; Proto-Oncogene Proteins B-raf; Proto-Oncogene Proteins p21(ras); PTEN Phosphohydrolase; Signal Transduction; TOR Serine-Threonine Kinases; Tumor Suppressor Protein p53journal article10.18632/oncotarget.5997265173542-s2.0-84951858024