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

Research output: Contribution to journalArticle

Abstract

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
Volume152
Issue number5
DOIs
StatePublished - Oct 7 2019

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Lung Neoplasms
Mutation
Second Primary Neoplasms
Single Nucleotide Polymorphism
Neoplasms
Lymph Nodes
Guidelines
Neoplasm Metastasis
Lung

Keywords

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

ASJC Scopus subject areas

  • Pathology and Forensic Medicine

Cite this

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title = "Clinical Validation of Discordant Trunk Driver Mutations in Paired Primary and Metastatic Lung Cancer Specimens",
abstract = "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.",
keywords = "Discordance, EGFR, KRAS, Lung cancers, Quality assessment, Trunk driver mutations",
author = "Tseng, {Li Hui} and {De Marchi}, Federico and Aparna Pallavajjalla and Erika Rodriguez and Rena Xian and Deborah Belchis and Gocke, {Christopher D.} and Eshleman, {James R.} and Peter Illei and Lin, {Ming Tseh}",
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AU - Tseng, Li Hui

AU - De Marchi, Federico

AU - Pallavajjalla, Aparna

AU - Rodriguez, Erika

AU - Xian, Rena

AU - Belchis, Deborah

AU - Gocke, Christopher D.

AU - Eshleman, James R.

AU - Illei, Peter

AU - Lin, Ming Tseh

PY - 2019/10/7

Y1 - 2019/10/7

N2 - 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.

AB - 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.

KW - Discordance

KW - EGFR

KW - KRAS

KW - Lung cancers

KW - Quality assessment

KW - Trunk driver mutations

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