Next Generation Sequencing A Novel Approach to Distinguish Multifocal Primary Lung Adenocarcinomas from Intrapulmonary Metastases. - PubMed - NCBI
J Mol Diagn. 2017 Aug 30. pii: S1525-1578(17)30327-6. doi: 10.1016/j.jmoldx.2017.07.006. [Epub ahead of print]
Next Generation Sequencing A Novel Approach to Distinguish Multifocal Primary Lung Adenocarcinomas from Intrapulmonary Metastases.
Abstract
Distinguishing between multiple lung primaries and intrapulmonary metastases is imperative for accurate staging. The American Joint Committee on Cancer (AJCC) criteria are routinely used for this purpose but can yield equivocal conclusions. We evaluated whether next generation sequencing (NGS) using the 50 gene AmpliSeq Cancer Hotspot Panel v2 can be used to facilitate this distinction. NGS was performed on known primary-metastatic pairs (8 patients) and multiple lung adenocarcinomas (11 patients). Primary-metastatic pairs showed high mutational concordance: Seven pairs shared mutations, and 1 was concordant for having no mutations. Driver mutations in KRAS (4), EGFR (2), and BRAF (1) were always concordant. Multiple lung tumors from 3 patients were completely concordant and, therefore, were predicted by NGS to be intrapulmonary metastases, whereas 8 had completely discordant mutations and, therefore, were predicted to be independent primaries. The NGS prediction correlated with the AJCC (eighth edition) prediction in all patients for whom the latter was unequivocal (8 of 11). Furthermore, it separated patients by overall survival: Patients with predicted multiple independent primaries by NGS had better survival than those with distant metastases (P = 0.016, log-rank test), whereas those with predicted intrapulmonary metastases showed no difference (P = 0.527). With further validation, the 50 gene panel has the potential to serve as an adjunct to the AJCC criteria, especially in patients for whom the latter is equivocal. Copyright © 2017. Published by Elsevier Inc.
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