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Targeted Sequencing Analysis of Pulmonary Adenocarcinoma with Multiple Synchronous Ground-glass/Lepidic Nodules.

Research paper by Eunhyang E Park, Soyeon S Ahn, Hyojin H Kim, Soo Young SY Park, Jisun J Lim, Hyun Jung HJ Kwon, Yeon Bi YB Han, Choon-Taek CT Lee, Sukki S Cho, Jin-Haeng JH Chung

Indexed on: 20 Aug '18Published on: 20 Aug '18Published in: Journal of Thoracic Oncology



Abstract

Lung adenocarcinoma (ADC) and synchronous ground-glass/lepidic (GG/L) nodules are considered a distinct disease entity in multiple synchronous lung cancers. Few studies have performed next-generation sequencing (NGS) analysis on these synchronous sequential lesions, and genetic alterations of GG/L nodules must be further investigated. We performed targeted sequencing in ADC with synchronous atypical adenomatous hyperplasia (AAH), adenocarcinoma in situ (AIS), or minimally invasive adenocarcinoma (MIA) from 16 patients. NGS was performed using a customized panel including 154 cancer-associated genes. Multiple synchronous lesions in the same patient showed different mutation profiles, and some shared identically mutated genes. In five patients harboring EGFR-mutant ADC, their synchronous GG/L nodules had EGFR mutation; however, none was observed in EGFR-wild type ADC. The average number of exonic mutations was 4.2, 5.4, 4.0, and 5.4 in AAH, AIS, MIA, and ADC, respectively. In each lesion type, various mutations including LRP1B, KRAS, EGFR, and BRAF were observed in AAH, and EGFR mutations were the most frequently observed in ADC. 80% of mutations with variant allele frequency (VAF) ≥ 20%, which contained driver gene mutations, were identified in ADC. Intratumoral heterogeneity of the genetic profile was found between the lepidic and invasive areas of ADC, but driver gene mutations were similar. This study suggested that ADC and synchronous GG/L nodules are genetically independent tumors. Intratumoral genetic heterogeneity of ADC was present, but driver gene mutations were homogeneously distributed. Driver gene mutations with high VAF were identified in the invasive tumor. These findings support the relevance of molecular characterization of lung ADC and synchronous GG/L nodules. Copyright © 2018 International Association for the Study of Lung Cancer. Published by Elsevier Inc. All rights reserved.