English  |  正體中文  |  简体中文  |  Items with full text/Total items : 12145/12927 (94%)
Visitors : 907320      Online Users : 905
RC Version 6.0 © Powered By DSPACE, MIT. Enhanced by NTU Library IR team.
Scope Tips:
  • please add "double quotation mark" for query phrases to get precise results
  • please goto advance search for comprehansive author search
    •  Adv. Search
    Home ‧ Login ‧ Upload ‧ Help ‧ About ‧ Administer Goto mobile version


    Please use this identifier to cite or link to this item: http://ir.nhri.org.tw/handle/3990099045/12293


    Title: Patterns of germline and somatic mutations in 16 genes associated with mismatch repair function or containing tandem repeat sequences
    Authors: Chang, SC;Lan, YT;Lin, PC;Yang, SH;Lin, CH;Liang, WY;Chen, WS;Jiang, JK;Lin, JK
    Contributors: Institute of Molecular and Genomic Medicine
    Abstract: BACKGROUND: We assumed that targeted next-generation sequencing (NGS) of mismatch repair-associated genes could improve the detection of driving mutations in colorectal cancers (CRC) with microsatellite instability (MSI) and microsatellite alterations at selected tetranucleotide repeats (EMAST) and clarify the somatic mutation patterns of CRC subtypes. MATERIAL AND METHODS: DNAs from tumors and white blood cells were obtained from 81 patients with EMAST(+)/MSI-high (MSI-H), 78 patients with EMAST(+)/microsatellite stable (MSS), and 72 patients with EMAST(-)/MSI-H. The germline and somatic mutations were analyzed with a 16-genes NGS panel. RESULTS: In total, 284 germline mutations were identified in 161 patients. The most common mutations were in EPCAM (24.8%), MSH6 (24.2%), MLH1 (21.7%), and AXIN2 (21.7%). Germline mutations of AXIN2, POLE, POLD1, and TGFBR2 also resulted in EMAST and MSI. EMAST(+)/MSI-H tumors had a significant higher mutation number (205.9 +/- 95.2 mut/MB) than tumors that were only EMAST(+) or MSI-H (118.6 +/- 64.2 and 106.2 +/- 54.5 mut/MB, respectively; both P < .001). In patients with AXIN2 germline mutations, the number of pathological somatic mutations in the tumors was significantly higher than those without AXIN2 germline mutations (176.7 +/- 94.2 mut/MB vs 139.6 +/- 85.0 mut/MB, P = .002). CONCLUSION: Next-generation sequencing could enhance the detection of familial CRC. The somatic mutation burden might result from not only the affected genes in germline mutations but also through the dysfunction of downstream effectors. The AXIN2 gene might associate with hypermutation in tumors. Further in vitro experiments to confirm the causal relationship is deserved.
    Date: 2020-01
    Relation: Cancer Medicine. 2020 Jan;9(2):476-486.
    Link to: http://dx.doi.org/10.1002/cam4.2702
    JIF/Ranking 2023: http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=NHRI&SrcApp=NHRI_IR&KeyISSN=2045-7634&DestApp=IC2JCR
    Cited Times(WOS): https://www.webofscience.com/wos/woscc/full-record/WOS:000498383700001
    Cited Times(Scopus): https://www.scopus.com/inward/record.url?partnerID=HzOxMe3b&scp=85075517692
    Appears in Collections:[其他] 期刊論文

    Files in This Item:

    File Description SizeFormat
    PUB31769227.pdf491KbAdobe PDF256View/Open


    All items in NHRI are protected by copyright, with all rights reserved.

    Related Items in TAIR

    DSpace Software Copyright © 2002-2004  MIT &  Hewlett-Packard  /   Enhanced by   NTU Library IR team Copyright ©   - Feedback