Clinical Validation of Discordant Trunk Driver Mutations in Paired Primary and Metastatic Lung Cancer Specimens

Li Hui Tseng, Federico De Marchi, Aparna Pallavajjalla, Erika Rodriguez, Rena Xian, Deborah Belchis, Christopher D. Gocke, James R. Eshleman, Peter Illei, Ming Tseh Lin

Research output: Contribution to journalArticlepeer-review

4 Scopus citations


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.

Original languageEnglish (US)
Pages (from-to)570-581
Number of pages12
JournalAmerican journal of clinical pathology
Issue number5
StatePublished - Oct 7 2019


  • Discordance
  • EGFR
  • KRAS
  • Lung cancers
  • Quality assessment
  • Trunk driver mutations

ASJC Scopus subject areas

  • Pathology and Forensic Medicine


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