期刊
MOLECULAR ONCOLOGY
卷 9, 期 9, 页码 1737-1743出版社
WILEY
DOI: 10.1016/j.molonc.2015.05.004
关键词
Failed analysis; Molecular oncology testing by NGS; Diagnostic biopsy; Site and type of biopsy; Number of cores; DNA degradation and purity
类别
资金
- Washington University Institute of Clinical and Translational Sciences from the National Center for Advancing Translational Sciences (NCATS) of the National Institutes of Health (NIH) [UL1TR000448]
Purpose: DNA analysis by NGS has become important to direct the clinical care of cancer patients. However, NGS is not successful in all cases, and the factors responsible for test failures have not been systematically evaluated. Materials and methods: A series of 1528 solid and hematolymphoid tumor specimens was tested by an NGS comprehensive cancer panel during 2012-2014. DNA was extracted and 2x101 bp paired-end sequence reads were generated on cancer-related genes utilizing Illumina HiSeq and MiSeq platforms. Results: Testing was unsuccessful in 343 (22.5%) specimens. The failure was due to insufficient tissue (INST) in 223/343 (65%) cases, insufficient DNA (INS-DNA) in 99/343 (28.9%) cases, and failed library (FL) in 21/343 (6.1%) cases. 87/99 (88%) of the INS-DNA cases had below 10 ng DNA available for testing. Factors associated with INST and INS-DNA failures were site of biopsy (SOB) and type of biopsy (TOB) (both p < 0.0001), and clinical setting of biopsy (CSB, initial diagnosis or recurrence) (p < 0.0001). Factors common to INST and FL were age of specimen (p <= 0.006) and tumor viability (p <= 0.05). Factors common to INSDNA and FL were DNA purity and DNA degradation (all p <= 0.005). In multivariate analysis, common predictors for INST and INS-DNA included CSB (p = 0.048 and p <0.0001) and TOB (both p < 0.003), respectively. SOB (p = 0.004) and number of cores (p = 0.001) were specific for INS-DNA, whereas TOB and DNA degradation were associated with FL (p = 0.04 and 0.02, respectively). Conclusions: Pre-analytical causes (INST and INS-DNA) accounted for about 90% of all failed cases; independent of test design. Clinical setting; site and type of biopsy; and number of cores used for testing all correlated with failure. Accounting for these factors at the time of tissue biopsy acquisition could improve the analytic success rate. (c) 2015 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据