Abstract:
:Next-generation sequencing (NGS) has recently been rapidly adopted in the molecular diagnosis of cancer, but it still faces some obstacles. In this study, 665 lung adenocarcinoma samples (558 TKI-naive and 107 TKI-relapsed samples) were interrogated using NGS, and the challenges and possible solutions of subjecting appropriate tissue samples to NGS testing were explored. The results showed that lower frequencies of HER2/BRAF/PIK3CA and acquired EGFR T790M mutations were observed in biopsy samples with <20% tumor cellularity than in those with ≥20%, but there were no significant differences in the frequencies of EGFR or KRAS mutations. Moreover, tumor heterogeneity was assessed by heterogeneity score (HS), which was calculated through multiplying by 2 the mutant allele frequency (MAF) of tumor cells. In TKI-naive samples, intratumor heterogeneity could occur in EGFR, KRAS, HER2, BRAF, and PIK3CA mutant tumors, but the degree was variable. Higher EGFR, but lower BRAF and PIK3CA HS values were observed compared with KRAS HS. In TKI-relapsed samples, analysis of concomitant sensitizing EGFR and T790M MAFs showed that intratumor heterogeneity was common in acquired EGFR T790M mutant tumors. The mutational status between primary and metastatic tumors was usually concordant, but KRAS, HER2, and PIK3CA HS were significantly higher in metastatic tumors than in primary tumors. Additionally, the discordance rate of mutational status in multifocal lung adenocarcinomas diagnosed as equivocal or multiple primary tumors was high. Together, our findings demonstrate that a comprehensive quality assessment is necessary during tissue process to mitigate the challenges of poor tumor cellularity, tumor heterogeneity, and multifocal clonally independent tumors.
journal_name
Mol Oncoljournal_title
Molecular oncologyauthors
Li W,Qiu T,Ling Y,Gao S,Ying Jdoi
10.1002/1878-0261.12190subject
Has Abstractpub_date
2018-05-01 00:00:00pages
677-689issue
5eissn
1574-7891issn
1878-0261journal_volume
12pub_type
杂志文章abstract::Deregulation of microRNAs contributes to the aberrant growth of hepatocellular carcinoma (HCC). Here, we showed that miR-634 expression was frequently decreased in HCC. Low miR-634 expression was significantly associated with larger tumor size, poorer tumor differentiation, advanced TNM stage, vascular invasion, absen...
journal_title:Molecular oncology
pub_type: 杂志文章
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journal_title:Molecular oncology
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journal_title:Molecular oncology
pub_type: 杂志文章
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journal_title:Molecular oncology
pub_type: 杂志文章,评审
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pub_type: 杂志文章
doi:10.1016/j.molonc.2013.05.002
更新日期:2013-10-01 00:00:00
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journal_title:Molecular oncology
pub_type: 杂志文章
doi:10.1016/j.molonc.2014.07.004
更新日期:2014-12-01 00:00:00
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journal_title:Molecular oncology
pub_type: 杂志文章,评审
doi:10.1016/j.molonc.2014.03.010
更新日期:2014-06-01 00:00:00
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pub_type: 杂志文章
doi:10.1002/1878-0261.12046
更新日期:2017-05-01 00:00:00
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journal_title:Molecular oncology
pub_type: 杂志文章,评审
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pub_type: 杂志文章
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journal_title:Molecular oncology
pub_type: 杂志文章
doi:10.1016/j.molonc.2014.03.022
更新日期:2014-07-01 00:00:00
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doi:10.1016/j.molonc.2014.06.008
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pub_type: 杂志文章
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更新日期:2021-01-01 00:00:00
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pub_type: 临床试验,杂志文章
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更新日期:2017-02-01 00:00:00
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更新日期:2020-12-13 00:00:00
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更新日期:2011-12-01 00:00:00
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pub_type: 杂志文章
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更新日期:2020-05-01 00:00:00