PMID- 32269691
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20200411
IS  - 1936-2625 (Electronic)
IS  - 1936-2625 (Linking)
VI  - 13
IP  - 3
DP  - 2020
TI  - Identifying a wide range of actionable variants using capture-based ultra-deep 
      targeted sequencing in treatment-naive patients with primary lung adenocarcinoma.
PG  - 525-535
AB  - Precision medicine requires accurate multi-gene clinical diagnostics. In current 
      clinical practice, the minimum confidence threshold for variant calling of 
      targeted next-generation sequencing (NGS) on surgical specimens is set to 2%-5%. 
      However, few studies have been conducted to identify a wide range of actionable 
      variants using capture-based ultra-deep targeted sequencing, which has limit of 
      detection (LOD) of 1%. The AmoyDx(R) Essential NGS panel for capture-based 
      ultra-deep targeted sequencing (dual-indexed sequencing adapters with UMIs) was 
      performed on 372 surgical specimens obtained from treatment-naive patients with 
      primary lung adenocarcinoma, to detect actionable somatic driver mutations 
      associated with each patient. Single-nucleotide variants, insertion/deletion 
      events, and rearrangements were reported. Amplification-refractory mutation 
      system (ARMS) assay and fluorescence in situ hybridization (FISH) were performed 
      for the validation of hotspot mutations in EGFR and ALK, ROS1, and RET fusions. 
      Potentially actionable variants were identified in 80.5% (352/437) of the 
      nonsynonymous variants that were able to be sequenced, and were most commonly 
      found in EGFR mutations (59.7%, 261/437), followed by KRAS mutations (5.5%, 
      24/437), PIK3CA mutations (3.7%, 16/437), ALK rearrangements (3.4%, 15/437), BRAF 
      mutations (2.7%, 12/437), ERBB2 mutations (2.5%, 11/437), and RET rearrangements 
      (2.3%, 10/437). A total of 7.2% (28/372) of the samples had multiple actionable 
      mutations. Among the 93 triple-negative cases, which did not harbor mutations in 
      EGFR, KRAS, or BRAF, gene fusions were detected in 26 cases (28%). Of the 328 
      samples, concordance of EGFR between the ARMS assay and NGS was observed in 318 
      samples (97.0%), and among 32 samples, concordance between ARMS/FISH test and NGS 
      for ALK/ROS1/RET fusion genes was observed in 30 samples (93.8%). Here, we 
      demonstrated that the capture-based ultra-deep targeted sequencing method, which 
      has a LOD of 1% to profile a wide range of actionable variants in surgical 
      specimens of treatment-naive lung adenocarcinoma patients, highlights the need 
      for treatment-naive patients to undergo genomic profiling.
CI  - IJCEP Copyright (c) 2020.
FAU - Chen, Lingfeng
AU  - Chen L
AD  - Shengli Clinical Medical College, Fujian Medical University Fuzhou, Fujian 
      Province, China.
AD  - Department of Pathology, Fujian Provincial Hospital Fuzhou, Fujian Province, 
      China.
FAU - Chen, Minyan
AU  - Chen M
AD  - Department of Breast Surgery, Fujian Medical University Union Hospital Fuzhou, 
      Fujian Province, China.
AD  - Department of General Surgery, Fujian Medical University Union Hospital Fuzhou, 
      Fujian Province, China.
FAU - Lin, Jie
AU  - Lin J
AD  - Shengli Clinical Medical College, Fujian Medical University Fuzhou, Fujian 
      Province, China.
AD  - Department of Pathology, Fujian Provincial Hospital Fuzhou, Fujian Province, 
      China.
FAU - Chen, Xiaoyan
AU  - Chen X
AD  - Shengli Clinical Medical College, Fujian Medical University Fuzhou, Fujian 
      Province, China.
AD  - Department of Pathology, Fujian Provincial Hospital Fuzhou, Fujian Province, 
      China.
FAU - Yu, Xunbin
AU  - Yu X
AD  - Shengli Clinical Medical College, Fujian Medical University Fuzhou, Fujian 
      Province, China.
AD  - Department of Pathology, Fujian Provincial Hospital Fuzhou, Fujian Province, 
      China.
FAU - Chen, Zhizhong
AU  - Chen Z
AD  - Shengli Clinical Medical College, Fujian Medical University Fuzhou, Fujian 
      Province, China.
AD  - Department of Pathology, Fujian Provincial Hospital Fuzhou, Fujian Province, 
      China.
FAU - Jin, Long
AU  - Jin L
AD  - Shengli Clinical Medical College, Fujian Medical University Fuzhou, Fujian 
      Province, China.
AD  - Department of Pathology, Fujian Provincial Hospital Fuzhou, Fujian Province, 
      China.
LA  - eng
PT  - Journal Article
DEP - 20200301
PL  - United States
TA  - Int J Clin Exp Pathol
JT  - International journal of clinical and experimental pathology
JID - 101480565
PMC - PMC7137022
OTO - NOTNLM
OT  - Next-generation sequencing
OT  - amplification-refractory mutation system
OT  - driver gene alterations
OT  - lung adenocarcinoma
OT  - unique molecular identifiers
COIS- None.
EDAT- 2020/04/10 06:00
MHDA- 2020/04/10 06:01
PMCR- 2020/03/01
CRDT- 2020/04/10 06:00
PHST- 2020/01/07 00:00 [received]
PHST- 2020/02/07 00:00 [accepted]
PHST- 2020/04/10 06:00 [entrez]
PHST- 2020/04/10 06:00 [pubmed]
PHST- 2020/04/10 06:01 [medline]
PHST- 2020/03/01 00:00 [pmc-release]
PST - epublish
SO  - Int J Clin Exp Pathol. 2020 Mar 1;13(3):525-535. eCollection 2020.