Clinical Validation of Discordant Trunk Driver Mutations in Paired Primary and Metastatic Lung Cancer Specimens
Journal
American Journal of Clinical Pathology
Journal Volume
152
Journal Issue
5
Pages
570-581
Date Issued
2019
Author(s)
De Marchi F.
Pallavajjalla A.
Rodriguez E.
Xian R.
Belchis D.
Gocke C.D.
Eshleman J.R.
Illei P.
Lin M.-T.
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. ? 2019 American Society for Clinical Pathology, 2019. All rights reserved.
Subjects
Discordance; EGFR; KRAS; Lung cancers; Quality assessment; Trunk driver mutations
SDGs
Other Subjects
B Raf kinase; epidermal growth factor receptor; B Raf kinase; BRAF protein, human; EGFR protein, human; epidermal growth factor receptor; KRAS protein, human; protein p21; Article; BRAF gene; brain metastasis; EGFR gene; gene mutation; human; human tissue; liver metastasis; lung cancer; lymph node metastasis; metastasis; next generation sequencing; oncogene K ras; oncogene N ras; pleura effusion; pleura metastasis; priority journal; retrospective study; Sanger sequencing; single nucleotide polymorphism; soft tissue metastasis; trunk driver mutation; adenocarcinoma; adenosquamous carcinoma; dna mutational analysis; gene frequency; genetics; genotype; high throughput sequencing; lung tumor; non small cell lung cancer; procedures; second cancer; Adenocarcinoma; Carcinoma, Adenosquamous; Carcinoma, Non-Small-Cell Lung; DNA Mutational Analysis; ErbB Receptors; Gene Frequency; Genotype; High-Throughput Nucleotide Sequencing; Humans; Lung Neoplasms; Neoplasms, Second Primary; Polymorphism, Single Nucleotide; Proto-Oncogene Proteins B-raf; Proto-Oncogene Proteins p21(ras)
Publisher
Oxford University Press
Type
journal article