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Genomic profiling of lung adenocarcinoma patients reveals therapeutic targets and confers clinical benefit when standard molecular testing is negative

Authors
 Sun Min Lim  ;  Eun Young Kim  ;  Hye Ryun Kim  ;  Siraj M. Ali  ;  Joel R. Greenbowe  ;  Hyo Sup Shim  ;  Hyun Chang  ;  Seungtaek Lim  ;  Soonmyung Paik  ;  Byoung Chul Cho 
Citation
 ONCOTARGET , Vol.7(17) : 24172-24178, 2016 
Journal Title
 ONCOTARGET 
Issue Date
2016
MeSH
Adenocarcinoma/drug therapy ; Adenocarcinoma/genetics* ; Adenocarcinoma/pathology ; Adult ; Aged ; Biomarkers, Tumor/genetics* ; Carcinoma, Non-Small-Cell Lung/drug therapy ; Carcinoma, Non-Small-Cell Lung/genetics* ; Carcinoma, Non-Small-Cell Lung/pathology ; Female ; Gene Expression Profiling* ; Genomics ; High-Throughput Nucleotide Sequencing/methods* ; Humans ; Lung Neoplasms/drug therapy ; Lung Neoplasms/genetics* ; Lung Neoplasms/pathology ; Male ; Middle Aged ; Molecular Targeted Therapy ; Mutation* ; Prognosis
Keywords
cancer gene test ; genomic profiling ; lung adenocarcinoma ; next-generation sequencing
Abstract
BACKGROUND: Identification of clinically relevant oncogenic drivers in advanced cancer is critical in selecting appropriate targeted therapy. Using next-generation sequencing (NGS)-based clinical cancer gene assay, we performed comprehensive genomic profiling (CGP) of advanced cases of lung adenocarcinoma. METHODS: Formalin-fixed paraffin-embedded tumors from 51 lung adenocarcinoma patients whose tumors previously tested negative for EGFR/KRAS/ALK by conventional methods were collected, and CGP was performed via hybridization capture of 4,557 exons from 287 cancer-related genes and 47 introns from 19 genes frequently rearranged in cancer. RESULTS: Genomic profiles of all 51 cases were obtained, with a median coverage of 564x and a total of 190 individual genomic alterations (GAs). GAs per specimen was a mean of 3.7 (range 0-10).Cancer genomes are characterized by 50% (80/190) non-synonymous base substitutions, 15% (29/190) insertions or deletion, and 3% (5/190) splice site mutation. TP53 mutation was the most common GAs (15%, n=29/190), followed by CDKN2A homozygous loss (5%, n=10/190), KRAS mutation (4%, n=8/190), EGFR mutation (4%, n=8/190) and MDM2 amplification (2%, n=5/190). As per NCCN guidelines, targetable GAs were identified in 16 patients (31%) (BRAF mutation [n=1], EGFR mutation [n=8], ERBB2 mutation [n=4], MET amplification [n=1], KIF5B-RET rearrangement [n=2], CCDC6-RET rearrangement [n=1], CD74-ROS1 rearrangement [n=1], EZR-ROS1 rearrangement [n=5], and SLC34A2-ROS1 rearrangement [n=1]). CONCLUSION: Fifty eight percent of patients wild type by standard testing for EGFR/KRAS/ALK have GAs identifiable by CGP that suggest benefit from target therapy. CGP used when standard molecular testing for NSCLC is negative can reveal additional avenues of benefit from targeted therapy.
Files in This Item:
T201603697.pdf Download
DOI
10.18632/oncotarget.8138
Appears in Collections:
1. College of Medicine (의과대학) > Dept. of Internal Medicine (내과학교실) > 1. Journal Papers
1. College of Medicine (의과대학) > BioMedical Science Institute (의생명과학부) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Pathology (병리학교실) > 1. Journal Papers
Yonsei Authors
Kim, Eun Young(김은영) ORCID logo https://orcid.org/0000-0002-3281-5744
Kim, Hye Ryun(김혜련) ORCID logo https://orcid.org/0000-0002-1842-9070
Paik, Soon Myung(백순명) ORCID logo https://orcid.org/0000-0001-9688-6480
Shim, Hyo Sup(심효섭) ORCID logo https://orcid.org/0000-0002-5718-3624
Lim, Sun Min(임선민)
Lim, Seung Taek(임승택)
Cho, Byoung Chul(조병철) ORCID logo https://orcid.org/0000-0002-5562-270X
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/152098
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