The DOI matches its Crossref record; 61 of the 61 references it cites were found in a registry or an index.
Sequence Artifacts in DNA from Formalin-Fixed Tissues: Causes and Strategies for Minimization
Abstract
BACKGROUND: Precision medicine is dependent on identifying actionable mutations in tumors. Accurate detection of mutations is often problematic in formalin-fixed paraffin-embedded (FFPE) tissues. DNA extracted from formalin-fixed tissues is fragmented and also contains DNA lesions that are the sources of sequence artifacts. Sequence artifacts can be difficult to distinguish from true mutations, especially in the context of tumor heterogeneity, and are an increasing interpretive problem in this era of massively parallel sequencing. Understanding of the sources of sequence artifacts in FFPE tissues and implementation of preventative strategies are critical to improve the accurate detection of actionable mutations. CONTENT: This mini-review focuses on DNA template lesions in FFPE tissues as the source of sequence artifacts in molecular analysis. In particular, fragmentation, base modification (including uracil and thymine deriving from cytosine deamination), and abasic sites are discussed as indirect or direct sources of sequence artifacts. We discuss strategies that can be implemented to minimize sequence artifacts and to distinguish true mutations from sequence artifacts. These strategies are applicable for the detection of actionable mutations in both single amplicon and massively parallel amplicon sequencing approaches. SUMMARY: Because FFPE tissues are usually the only available material for DNA analysis, it is important to maximize the accurate informational content from FFPE DNA. Careful consideration of each step in the work flow is needed to minimize sequence artifacts. In addition, validation of actionable mutations either by appropriate experimental design or by orthogonal methods should be considered.
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Cites
Sequencing technologies – the next generation
Metzker, M. L. (2010) · Nature Reviews Genetics · doi:10.1038/nrg2626 · Cited by 7,066
EGFR Mutation and Resistance of Non–Small-Cell Lung Cancer to Gefitinib
Kobayashi, S., Boggon, T. J., Dayaram, T., Jänne, P. A., Kocher, O., Meyerson, M., Johnson, B. E., Eck, M. J., Tenen, D. G., & Halmos, B. (2005) · New England Journal of Medicine · doi:10.1056/nejmoa044238 · Cited by 3,964
K-ras Mutations and Benefit from Cetuximab in Advanced Colorectal Cancer
Karapetis, C. S., Khambata-Ford, S., Jonker, D. J., O'Callaghan, C. J., Tu, D., Tebbutt, N. C., Simes, R. J., Chalchal, H., Shapiro, J. D., Robitaille, S., et al. (2008) · New England Journal of Medicine · doi:10.1056/nejmoa0804385 · Cited by 3,622
Mapping short DNA sequencing reads and calling variants using mapping quality scores
Li, H., Ruan, J., & Durbin, R. (2008) · Genome Research · doi:10.1101/gr.078212.108 · Cited by 2,638
Emergence of KRAS mutations and acquired resistance to anti-EGFR therapy in colorectal cancer
Misale, S., Yaeger, R., Hobor, S., Scala, E., Janakiraman, M., Liska, D., Valtorta, E., Schiavo, R., Buscarino, M., Siravegna, G., et al. (2012) · Nature · doi:10.1038/nature11156 · Cited by 1,889
Erlotinib in Lung Cancer — Molecular and Clinical Predictors of Outcome
Tsao, M.-S., Sakurada, A., Cutz, J.-C., Zhu, C.-Q., Kamel-Reid, S., Squire, J., Lorimer, I., Zhang, T., Liu, N., Daneshmand, M., et al. (2005) · New England Journal of Medicine · doi:10.1056/nejmoa050736 · Cited by 1,830
Rate of depurination of native deoxyribonucleic acid
Lindahl, T., & Nyberg, B. (1972) · Biochemistry · doi:10.1021/bi00769a018 · Cited by 1,556
Absolute quantification by droplet digital PCR versus analog real-time PCR
Hindson, C. M., Chevillet, J. R., Briggs, H. A., Gallichotte, E. N., Ruf, I. K., Hindson, B. J., Vessella, R. L., & Tewari, M. (2013) · Nature Methods · doi:10.1038/nmeth.2633 · Cited by 1,488
Detection and quantification of rare mutations with massively parallel sequencing
Kinde, I., Wu, J., Papadopoulos, N., Kinzler, K. W., & Vogelstein, B. (2011) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1105422108 · Cited by 1,144
Detection of ultra-rare mutations by next-generation sequencing
Schmitt, M. W., Kennedy, S. R., Salk, J. J., Fox, E. J., Hiatt, J. B., & Loeb, L. A. (2012) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1208715109 · Cited by 1,047
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Metadata
- Authors
- Do, H., & Dobrovic, A.
- Venue
- Clinical Chemistry
- Publisher
- Oxford University Press (OUP)
- Published
- 2015-01-01
- Volume
- 61
- Issue
- 1
- Pages
- 64-71
- ISSN
- 0009-9147 (ISSN-L)
- 1530-8561
- OpenAlex
- W2154448561
- Cited by
- 572
- References
- 61
- FWCI
- 7.58
- Type
- journal article
- Language
- en
- Open access
- closed
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