國家衛生研究院 NHRI:Item 3990099045/11840
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    題名: The clinical features and genomic landscape of elevated microsatellite alterations at selected tetranucleotide repeats (EMAST) in patients with colorectal cancer
    作者: Chen, MH;Chang, SC;Lin, PC;Yang, SH;Lin, CC;Lan, YT;Lin, HH;Lin, CH;Liang, WY;Chen, WS;Jiang, JK;Lin, JK
    貢獻者: Institute of Molecular and Genomic Medicine
    摘要: Background: Elevated microsatellite alterations at selected tetranucleotide repeats (EMAST) is another form of microsatellite instability (MSI) at tetranucleotide repeats and has emerged as a new potential biomarker in multiple cancers. In colorectal cancer (CRC), the clinical implications and mutation spectrum of EMAST remain inconclusive. Methods: We evaluated 1,505 CRC cases using five markers (D20S82, D20S85, D8S321, D9S242 and MYCL1) for EMAST and the Bethesda panel for MSI status. Most commonly mutations involved in CRCs were identified by MassArray Assay. DNA repair genes were analyzed by Next-Generation Sequencing (NGS). Clinical characteristics and prognostic relevance were correlated with EMAST. All statistics were assessed by SPSS software (version 16.0). Results: We first identified the optimal definition of EMAST-positive as tumors showing framshifts in at least two tetranucleotide markers. According to this definition, the frequencies of EMAST was 159 (10.6%) out of 1,505 CRC cases with unique clinical features with female predominant (p = 0.017), a higher prevalence in proximal colon (p < 0.001), a tendency of early stage (p = 0.002), poorly differentiated (p < 0.001), mucinous histology (p = 0.001) and highly associated with MSI (p < 0.001). Mutation spectrum in EMAST- positive tumors showed a higher incidence of PI3KCA mutations (p = 0.003), BRAF mutations (p < 0.001), TGFßR mutations (p < 0.001), PTEN mutations (p = 0.001) and AKT1 mutations (p = 0.04) compared with EMAST– negative tumors. Furthermore, Compared with EMAST positive alone or MSI alone tumors, both EMAST positive and MSI-H tumors had higher mutation rates in MSH6, MSH3, PMS2, EXO1 genes (p < 0.001, p = 0.005, p = 0.001, p = 0.027) and MLH1, MSH6, and EXO1 genes (p = 0.019, p = 0.005, p = 0.046). Finally, EMAST-positive tumors was a good prognostic factor in early stage CRC (p = 0.002), but not stage IV CRC (p = 0.920). Patient with both EMAST positive and MSI-H had best outcome compared with other patients (p < 0.001). Conclusions: The EMAST defines a unique molecular subtype of CRC.
    日期: 2018-10
    關聯: Annals of Oncology. 2018 Oct;29(Suppl. 8):178.
    Link to: https://doi.org/10.1093/annonc/mdy281.077
    JIF/Ranking 2023: http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=NHRI&SrcApp=NHRI_IR&KeyISSN=0923-7534&DestApp=IC2JCR
    Cited Times(WOS): https://www.webofscience.com/wos/woscc/full-record/WOS:000459277301113
    Cited Times(Scopus): https://www.scopus.com/inward/record.url?partnerID=HzOxMe3b&scp=85081529115
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