Journal
AMERICAN JOURNAL OF CLINICAL PATHOLOGY
Volume 152, Issue 5, Pages 570-581Publisher
OXFORD UNIV PRESS INC
DOI: 10.1093/ajcp/aqz077
Keywords
Discordance; Trunk driver mutations; Lung cancers; KRAS; EGFR; Quality assessment
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Funding
- National Institute of Health-National Cancer Institute of the United States [1UM1CA186691-01]
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Objectives: To propose an operating procedure for validation of discordant trunk driver mutations. Methods: Concordance of trunk drivers was examined by next-generation sequencing in 15 patients with two to three metastatic lung cancers and 32 paired primary and metastatic lung cancers. Results: Tissue identity was confirmed by genotyping 17 single-nucleotide polymorphisms within the panel. All except three pairs showed concordant trunk drivers. Quality assessment conducted in three primary and metastatic pairs with discordant trunk drivers indicates metastasis from a synchronous or remote lung primary in two patients. Review of literature revealed high discordant rates of EGFR and KRAS mutations, especially when Sanger sequencing was applied to examine primary and lymph node metastatic tumors. Conclusions: Trunk driver mutations are highly concordant in primary and metastatic tumors. Discordance of trunk drivers, once confirmed, may suggest a second primary cancer. Guidelines are recommended to establish standard operating procedures for validation of discordant trunk drivers.
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